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Lyme Arthritis: Accurate Diagnosis Improves Prognosis
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS
Lyme Arthritis: Accurate Diagnosis Improves Prognosis
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS
Lyme Arthritis: Accurate Diagnosis Improves Prognosis
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
Most cases of Lyme arthritis are brief and can be managed successfully with oral antibiotics, according to a recent review article in the February issue of the Journal of the American Academy of Orthopaedic Surgeons.
A delayed or missed diagnosis, however, increases the likelihood that the inflammatory response triggered by infection with the tick-borne Borrelia burgdorferi spirochete will lead to permanent joint damage, according to Dr. Brian G. Smith of Yale University in New Haven, Conn., and colleagues. For this reason, they stressed, Lyme arthritis "should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic."
Timely diagnosis of Lyme arthritis is often hampered by the fact that the clinical presentation – including recurrent episodes of joint swelling, typically in large joints such as the knee, but also possibly in the ankle, wrist, hip, or elbow; large effusions that may be out of proportion to patients' complaints; and, occasionally, fever – can be similar to that of inflammatory arthritides or acute bacterial septic arthritis, especially in children, the authors wrote (J. Am. Acad. Orthop. Surg. 2011.19:91-100).
In patients with acute symptoms, physicians "may be asked to evaluate a child who presents to the emergency department with an acutely swollen, tender joint as well as other Lyme disease–related symptoms that may be indicative of bacterial septic arthritis, such as malaise or irritability with or without fever and limited weight bearing." Joint-fluid analyses in patients with both diseases frequently reveal "strikingly elevated joint leukocyte counts," occasionally leading to unnecessary surgical joint debridement in patients erroneously diagnosed with septic arthritis, they stated.
Because of the similar and overlapping presentations and the fact that an accurate, reliable rapid test for Lyme disease is not widely available, "clinical and laboratory variables should be used as tools in the diagnostic armamentarium," the authors wrote. Although these variables have not been definitively established, the findings of a retrospective comparison of the clinical indications and laboratory results of children who presented to the emergency department with serologically confirmed Lyme arthritis and those who presented with septic arthritis identified a negative history of fever, knee involvement, and normal C-reactive protein (CRP) levels as important predictors of Lyme arthritis (Pediatrics. 2009; 123:959-65).
More recently, the authors of the current study conducted a review of children who presented to their institution with joint effusion, and determined that – relative to patients with septic arthritis – those with Lyme arthritis "had a lower average peripheral white blood count, lower percentage of neutrophils in the differential, were less likely to present with a temperature [greater than] 101.5[° F], and were less likely to refuse to bear weight on the affected extremity," they wrote. "No statistically significant difference existed between the two groups with regard to erythrocyte sedimentation rate and CRP level" (J. Bone Joint Surg. Am. 2011;93:252-60).
Following an accurate diagnosis, "Lyme arthritis has an excellent prognosis with appropriate management," the authors stressed. In adults without neurologic involvement, this includes a 28-day course of 100-mg doxycycline twice daily, 500-mg amoxicillin three times daily, or 500-mg cefuroxime axetil twice daily. The recommended treatment for children is a 28-day course of 50-mg/kg amoxicillin divided into three doses daily, 30-mg/kg cefuroxime axetil divided into two doses daily, or – for patients aged 8 years or older – 4-mg/kg doxycycline divided into two doses daily, they wrote.
Patients with mild persistent or recurrent synovitis after the initial therapeutic course should repeat the 28-day antibiotic course, whereas those with moderate to severe persistent arthritis should begin a 2-week or 4-week course of parenteral antibiotics, the authors wrote, noting that those with persistent symptoms after two treatment courses should undergo polymerase chain reaction (PCR) testing. Patients with positive PCR results should repeat the oral antibiotic regimen for 28 days, whereas those with negative PCR results may be treated with NSAIDs and intra-articular corticosteroids, they stated. Hydroxychloroquine, which may have antispirochetal and anti-inflammatory effects, may be used in the negative PCR patients, and "there may be a role for certain disease-modifying antirheumatic agents in the management of chronic Lyme arthritis, but experience with their use in this setting is limited," they said.
For patients with antibiotic-refractory Lyme arthritis, "arthroscopic synovectomy is a reasonable treatment option," the authors wrote, alluding to small case series demonstrating marked resolution of joint inflammation and maintained improvement follow the surgical procedure in treatment-refractory patients.
Increased awareness of the symptoms and risk factors associated with Lyme disease is needed to improve detection and treatment of Lyme arthritis, and further research is warranted to better distinguish between Lyme arthritis and other types of arthritis in symptomatic patients because the management approaches are inherently different, the authors concluded.
Dr. Smith disclosed a financial relationship with Stryker. Study coauthor Dr. Eugene D. Shapiro, also of Yale University, disclosed affiliations with the American Board of Pediatrics' Board on Infectious Diseases, and the American Lyme Disease Foundation.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS
Conflicting CCSVI Data Lead to Call for New Research, United Message
Multiple sclerosis patients and endovascular interventionalists were elated when Italian researchers reported in 2009 that they had found evidence of chronic cerebrospinal venous insufficiency in nearly every MS patient they had studied and that in many cases, balloon angioplasty and sometimes stent placement of central thoracic veins reduced or eliminated signs of the disease. Neurologists, on the other hand, suggested that hope might be eclipsing reason in the rush to advocate the vascular procedure, given the single-center study’s small sample size and nonrandomized, uncontrolled design.
The opposing perspectives incited an apparent turf war within the MS community fueled by a firestorm of accusations, with both sides going for the jugular, according to Dr. Jack Burks, chief medical officer of the Multiple Sclerosis Association of America. At issue, he said, is the validity not only of the study results but also of the underlying hypothesis that toxic iron overload in the brain due to chronic cerebrospinal venous insufficiency (CCSVI) might have a primary role in the pathogenesis of MS – a hypothesis that contradicts the compelling body of evidence suggesting that MS is primarily an autoimmune condition.
On one side of the debate are the MS patients and endovascular interventionalists, dubbed the "liberators" by Dr. Burks because of their unflappable advocacy for what has become known as the liberation procedure – the endovascular surgery designed to open the lesions causing the venous insufficiency, he said. On the other side are the neurologists and MS societies, whom he lightheartedly calls the CCSVI nihilists because of their outspoken criticism of the surgery in the absence of more robust, conclusive scientific evidence.
"Neurologists believe the interventionalists are overstating the possible value of CCSVI and that commercial interests are overriding scientific inquiry," according to Dr. Burks, a neurologist and clinical professor of medicine at the University of Nevada, Reno. Patients, armed with anecdotal evidence downloaded from the Internet, are certain that CCSVI surgery is the miracle they’ve been waiting for and perceive the hesitancy of U.S. and Canadian neurologists to embrace the treatment as evidence of a possible conspiracy with pharmaceutical companies who stand to lose billions of dollars if the surgery becomes a first-line treatment, he said. Further, he noted, advocates of CCSVI claim that neurologists who refuse patients’ demands for diagnostic testing and surgical referral for CCSVI are jeopardizing the safety of those patients, who are traveling to foreign countries such as Poland, Bulgaria, Mexico, Costa Rica, and India to get the care that they cannot receive in North America.
Both camps point to the much publicized case of a Canadian MS patient who traveled to Costa Rica for jugular vein angioplasty and died from a ruptured vessel as evidence that supports their respective positions, said Dr. Burks.
To date, the majority of the evidence regarding CCSVI diagnosis and treatment in MS is inconsistent, and can be confusing, Dr. Burks noted. In the initial study, Dr. Paolo Zamboni of the University of Ferrara in Italy, and colleagues, used Doppler ultrasound to examine venous drainage of the brain and spinal cord in 65 patients with different types of MS and 235 controls without MS and observed abnormal venous flow in all of the MS patients and none of the controls. The patterns of venous obstruction differed depending on MS stage and course, although there was no apparent relationship between disease severity and extent of venous obstruction, and MS treatment status did not influence the signs of CCSVI in any of the patients, the authors wrote (J. Neurol. Neurosurg. Psychiatry 2009;80:392-9).
The researchers went on to conduct an open pilot study to determine whether percutaneous transluminal angioplasty could safely and effectively treat the narrowing of the extracranial cerebrospinal veins in the 65 MS patients in which the condition was observed – 35 with relapsing-remitting MS, 20 with secondary progressive MS, and 10 with primary progressive MS. They reported significant improvements in MS clinical outcome measures, significant reductions in new brain lesions on MRI, and significant reductions in the number of relapses experienced by some of the patients.
The findings were limited, however, not only by the study design, but also by the fact that patients remained on their disease-modifying antirheumatic drug therapy during the study period and the timing and type of MRI scans varied among the patients, according to the authors. They also noted that restenosis of the internal jugular veins occurred in nearly half of the patients (J. Vasc. Surg. 2009;50:1348-58).
Since the initial paper, a number of CCSVI studies of various designs have been undertaken, with contradictory results. Following are some of the investigations reported within the past year:
• Researchers at the University of Buffalo found that up to 62% of the 280 patients with MS enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation study – the first randomized clinical trial to evaluate MS patients for CCSVI – had the characteristic narrowing of the extracranial veins compared with approximately 22% of 220 healthy controls. While the results, which were reported at the annual meeting of the American Academy of Neurology, did not establish causation, they showed "that narrowing of the extracranial veins, at the very least, is an important association in multiple sclerosis," principal investigator Dr. Robert Zivadinov said in a statement. He acknowledged that the finding of vascular narrowing in nearly a quarter of the healthy controls warranted additional investigation.
• In an open-label study of extracranial Doppler criteria of CCSVI in 70 MS patients in Poland – 49 with relapsing-remitting MS, 5 with primary progressive MS, and 16 with secondary progressive MS – investigators detected at least two of four extracranial criteria in 90% of the patients. They concluded that, while the extracranial abnormalities could exist in various combinations, "the most common pathology in our patients was the presence of an inverted valve or another pathologic structure [like membranaceous or netlike septum] in the area of junction of the [internal jugular vein] with the brachiocephalic vein (Int. Angiol. 2010;29:109-14).
• A comparison of the internal jugular vein hemodynamics and morphology in 25 patients with MS and 25 controls identified abnormal findings in 92% of the MS patients and 24% of the controls, and evidence of CCSVI in 84% of the MS patients and none of the controls, leading the investigators to conclude that both hemodynamic abnormalities and morphologic changes in the internal jugular vein "are strongly associated with MS" (Int. Angiol. 2010;29:115-20).
• An extended extra- and transcranial color-coded sonography study in 56 MS patients and 20 controls detected no internal jugular vein stenosis and normal blood flow direction in all but 1 patient. There were no between-group differences in intracranial veins and during Valsalva maneuver, and none of the patients fulfilled more than one CCSVI criterion, according to the authors. They concluded that their findings "challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS" (Ann. Neurol. 2010;68:173-83).
• Swedish investigators used phase-contrast MRI to study 21 relapsing-remitting MS patients and 20 healthy controls and found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux between the two groups. Although contrast-enhanced MR angiography showed internal jugular vein stenosis in 3 of the 21 MS patients, the authors stated they found no evidence "confirming the suggested vascular multiple sclerosis hypothesis" (Ann. Neurol. 2010;68:255-9).
• The authors of an MR venography and flow quantification study in The Netherlands compared the intracranial and extracranial venous anatomy and the intracerebral venous flow profiles of 20 MS patients and 20 age- and gender-matched controls, with image analysis performed by blinded interventional neuroradiologists. They identified venous system anomalies in 50% of the MS patients and 40% of the healthy controls and no venous backflow in either group. "Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions," the authors wrote (J. Neurol. Neurosurg. Psychiatry 2010 Oct. 27 [doi: 10.1136/jnnp.2010.223479]).
• Italian researchers investigating the occurrence of CCSVI in 50 consecutive patients with clinically isolated syndromes suggestive of MS reviewed the patients’ extracranial and transcranial venous echo-color Doppler sonographs and compared the findings to those of 50 age- and gender matched healthy controls as well as those of 60 patients with transient global amnesia (TGA) and 60 healthy controls matched to the TGA patients. They found extracranial Doppler sonographic abnormalities in 52% of patients with possible MS, 68.3% of patients with TGA, and 31.8% of the healthy controls. While eight of the patients with possible MS fulfilled the CCSVI criteria, selective phlebography showed no venous anomalies in seven of them. The authors concluded that there was no evidence of CCSVI at MS onset but recommended further studies to "clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS" (Ann. Neurol. 2011;69:90-99).
Not only do the findings of this study challenge the hypothesis that CCSVI plays a role in the pathogenesis of MS, they suggest that some patients may be getting unnecessary surgery, according to lead author Dr. Claudio Baracchini of the University of Padua, Italy. "The few patients [in this study] with venous anomalies suggesting a CCSVI pattern had normal cerebral venous hemodynamics and all of the patients who underwent selective venography had predominantly normal findings," he said in an interview. For such patients, the surgery is "unjustified and associated with unnecessary risk," he stressed.
Despite the media focus on the professional divide sparked by the CCSVI controversy, most in the scientific community agree that more research is needed before interventional surgery for CCSVI can be routinely recommended.
In a position statement, the Society of Interventional Radiology stated that at present, the published literature is "inconclusive on whether CCSVI is a clinically important factor in the development and/or progression of MS, and on whether balloon angioplasty and/or stent placement are clinically effective in patients with MS" (J. Vasc. Interv. Radiol. 2010;21:1335-7).
Additionally, in a commentary on the treatment of CCSVI, representatives of the Cardiovascular and Interventional Radiological Society of Europe acknowledged that although several centers worldwide are promoting and performing balloon dilatation, with or without stenting for CCSVI, "no trial data are available, and there is currently no randomized controlled trial [RCT] in progress." Further, anecdotal evidence and patient testimonies on the Internet are not a sound basis to offer a new treatment "which could have possible procedure-related complications to an often desperate patient population," they wrote. "We believe that until real scientific data are available for CCSVI and balloon dilatation, this treatment should not be offered to MS patients outside of a well designed clinical trial" (Cardiovasc. Intervent. Radiol. 2011;34:1-2).
Toward that end, the National Multiple Sclerosis Society of the United States and the MS Society of Canada have pledged $2.4 million in support of seven CCSVI research studies, including projects designed to evaluate venous abnormalities in children and teens with MS, patients with early and late stage MS, and those at risk for MS. An international review panel comprising radiologists, vascular surgeons, and neurologists evaluated research applications via an expedited review process and chose those that "combined the strongest science with the research goals necessary to most quickly determine the scope and meaning or reported abnormalities in blood drainage from the brain and spinal cord in MS," according to the societies. "It is hoped these findings will provide clarity regarding the need for next-step therapeutic trials to correct such blockages as MS societies around the world pursue this CCSVI lead."
In a presentation at the annual International Symposium of Endovascular Therapy in January, Dr. Burks outlined the critical issues related to crafting a united CCSVI message with multidisciplinary support, which include the best CCSVI diagnostic tests and outcomes; treatment standards and successful outcomes; diagnostic criteria; standards for qualified CCSVI specialists and treatment centers; uniform institutional review board requirements; standards, by discipline, for follow-up care; and criteria for retreatment and procedural standards.
Additionally, "we need to establish a CCSVI patient registry that documents outcomes and adverse events, as well as other relevant data, and disseminate that document widely to all groups," Dr. Burks said. Doing so will go far toward mending the fractious community and directing energy toward optimal patient care, he stated.
Dr. Burks disclosed financial relationships with Acorda, Allergan, Avanir, Bayer, Biogen Idec, Novartis, and Serono. Dr. Baracchini disclosed having no relevant financial relationships.
Multiple sclerosis patients and endovascular interventionalists were elated when Italian researchers reported in 2009 that they had found evidence of chronic cerebrospinal venous insufficiency in nearly every MS patient they had studied and that in many cases, balloon angioplasty and sometimes stent placement of central thoracic veins reduced or eliminated signs of the disease. Neurologists, on the other hand, suggested that hope might be eclipsing reason in the rush to advocate the vascular procedure, given the single-center study’s small sample size and nonrandomized, uncontrolled design.
The opposing perspectives incited an apparent turf war within the MS community fueled by a firestorm of accusations, with both sides going for the jugular, according to Dr. Jack Burks, chief medical officer of the Multiple Sclerosis Association of America. At issue, he said, is the validity not only of the study results but also of the underlying hypothesis that toxic iron overload in the brain due to chronic cerebrospinal venous insufficiency (CCSVI) might have a primary role in the pathogenesis of MS – a hypothesis that contradicts the compelling body of evidence suggesting that MS is primarily an autoimmune condition.
On one side of the debate are the MS patients and endovascular interventionalists, dubbed the "liberators" by Dr. Burks because of their unflappable advocacy for what has become known as the liberation procedure – the endovascular surgery designed to open the lesions causing the venous insufficiency, he said. On the other side are the neurologists and MS societies, whom he lightheartedly calls the CCSVI nihilists because of their outspoken criticism of the surgery in the absence of more robust, conclusive scientific evidence.
"Neurologists believe the interventionalists are overstating the possible value of CCSVI and that commercial interests are overriding scientific inquiry," according to Dr. Burks, a neurologist and clinical professor of medicine at the University of Nevada, Reno. Patients, armed with anecdotal evidence downloaded from the Internet, are certain that CCSVI surgery is the miracle they’ve been waiting for and perceive the hesitancy of U.S. and Canadian neurologists to embrace the treatment as evidence of a possible conspiracy with pharmaceutical companies who stand to lose billions of dollars if the surgery becomes a first-line treatment, he said. Further, he noted, advocates of CCSVI claim that neurologists who refuse patients’ demands for diagnostic testing and surgical referral for CCSVI are jeopardizing the safety of those patients, who are traveling to foreign countries such as Poland, Bulgaria, Mexico, Costa Rica, and India to get the care that they cannot receive in North America.
Both camps point to the much publicized case of a Canadian MS patient who traveled to Costa Rica for jugular vein angioplasty and died from a ruptured vessel as evidence that supports their respective positions, said Dr. Burks.
To date, the majority of the evidence regarding CCSVI diagnosis and treatment in MS is inconsistent, and can be confusing, Dr. Burks noted. In the initial study, Dr. Paolo Zamboni of the University of Ferrara in Italy, and colleagues, used Doppler ultrasound to examine venous drainage of the brain and spinal cord in 65 patients with different types of MS and 235 controls without MS and observed abnormal venous flow in all of the MS patients and none of the controls. The patterns of venous obstruction differed depending on MS stage and course, although there was no apparent relationship between disease severity and extent of venous obstruction, and MS treatment status did not influence the signs of CCSVI in any of the patients, the authors wrote (J. Neurol. Neurosurg. Psychiatry 2009;80:392-9).
The researchers went on to conduct an open pilot study to determine whether percutaneous transluminal angioplasty could safely and effectively treat the narrowing of the extracranial cerebrospinal veins in the 65 MS patients in which the condition was observed – 35 with relapsing-remitting MS, 20 with secondary progressive MS, and 10 with primary progressive MS. They reported significant improvements in MS clinical outcome measures, significant reductions in new brain lesions on MRI, and significant reductions in the number of relapses experienced by some of the patients.
The findings were limited, however, not only by the study design, but also by the fact that patients remained on their disease-modifying antirheumatic drug therapy during the study period and the timing and type of MRI scans varied among the patients, according to the authors. They also noted that restenosis of the internal jugular veins occurred in nearly half of the patients (J. Vasc. Surg. 2009;50:1348-58).
Since the initial paper, a number of CCSVI studies of various designs have been undertaken, with contradictory results. Following are some of the investigations reported within the past year:
• Researchers at the University of Buffalo found that up to 62% of the 280 patients with MS enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation study – the first randomized clinical trial to evaluate MS patients for CCSVI – had the characteristic narrowing of the extracranial veins compared with approximately 22% of 220 healthy controls. While the results, which were reported at the annual meeting of the American Academy of Neurology, did not establish causation, they showed "that narrowing of the extracranial veins, at the very least, is an important association in multiple sclerosis," principal investigator Dr. Robert Zivadinov said in a statement. He acknowledged that the finding of vascular narrowing in nearly a quarter of the healthy controls warranted additional investigation.
• In an open-label study of extracranial Doppler criteria of CCSVI in 70 MS patients in Poland – 49 with relapsing-remitting MS, 5 with primary progressive MS, and 16 with secondary progressive MS – investigators detected at least two of four extracranial criteria in 90% of the patients. They concluded that, while the extracranial abnormalities could exist in various combinations, "the most common pathology in our patients was the presence of an inverted valve or another pathologic structure [like membranaceous or netlike septum] in the area of junction of the [internal jugular vein] with the brachiocephalic vein (Int. Angiol. 2010;29:109-14).
• A comparison of the internal jugular vein hemodynamics and morphology in 25 patients with MS and 25 controls identified abnormal findings in 92% of the MS patients and 24% of the controls, and evidence of CCSVI in 84% of the MS patients and none of the controls, leading the investigators to conclude that both hemodynamic abnormalities and morphologic changes in the internal jugular vein "are strongly associated with MS" (Int. Angiol. 2010;29:115-20).
• An extended extra- and transcranial color-coded sonography study in 56 MS patients and 20 controls detected no internal jugular vein stenosis and normal blood flow direction in all but 1 patient. There were no between-group differences in intracranial veins and during Valsalva maneuver, and none of the patients fulfilled more than one CCSVI criterion, according to the authors. They concluded that their findings "challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS" (Ann. Neurol. 2010;68:173-83).
• Swedish investigators used phase-contrast MRI to study 21 relapsing-remitting MS patients and 20 healthy controls and found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux between the two groups. Although contrast-enhanced MR angiography showed internal jugular vein stenosis in 3 of the 21 MS patients, the authors stated they found no evidence "confirming the suggested vascular multiple sclerosis hypothesis" (Ann. Neurol. 2010;68:255-9).
• The authors of an MR venography and flow quantification study in The Netherlands compared the intracranial and extracranial venous anatomy and the intracerebral venous flow profiles of 20 MS patients and 20 age- and gender-matched controls, with image analysis performed by blinded interventional neuroradiologists. They identified venous system anomalies in 50% of the MS patients and 40% of the healthy controls and no venous backflow in either group. "Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions," the authors wrote (J. Neurol. Neurosurg. Psychiatry 2010 Oct. 27 [doi: 10.1136/jnnp.2010.223479]).
• Italian researchers investigating the occurrence of CCSVI in 50 consecutive patients with clinically isolated syndromes suggestive of MS reviewed the patients’ extracranial and transcranial venous echo-color Doppler sonographs and compared the findings to those of 50 age- and gender matched healthy controls as well as those of 60 patients with transient global amnesia (TGA) and 60 healthy controls matched to the TGA patients. They found extracranial Doppler sonographic abnormalities in 52% of patients with possible MS, 68.3% of patients with TGA, and 31.8% of the healthy controls. While eight of the patients with possible MS fulfilled the CCSVI criteria, selective phlebography showed no venous anomalies in seven of them. The authors concluded that there was no evidence of CCSVI at MS onset but recommended further studies to "clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS" (Ann. Neurol. 2011;69:90-99).
Not only do the findings of this study challenge the hypothesis that CCSVI plays a role in the pathogenesis of MS, they suggest that some patients may be getting unnecessary surgery, according to lead author Dr. Claudio Baracchini of the University of Padua, Italy. "The few patients [in this study] with venous anomalies suggesting a CCSVI pattern had normal cerebral venous hemodynamics and all of the patients who underwent selective venography had predominantly normal findings," he said in an interview. For such patients, the surgery is "unjustified and associated with unnecessary risk," he stressed.
Despite the media focus on the professional divide sparked by the CCSVI controversy, most in the scientific community agree that more research is needed before interventional surgery for CCSVI can be routinely recommended.
In a position statement, the Society of Interventional Radiology stated that at present, the published literature is "inconclusive on whether CCSVI is a clinically important factor in the development and/or progression of MS, and on whether balloon angioplasty and/or stent placement are clinically effective in patients with MS" (J. Vasc. Interv. Radiol. 2010;21:1335-7).
Additionally, in a commentary on the treatment of CCSVI, representatives of the Cardiovascular and Interventional Radiological Society of Europe acknowledged that although several centers worldwide are promoting and performing balloon dilatation, with or without stenting for CCSVI, "no trial data are available, and there is currently no randomized controlled trial [RCT] in progress." Further, anecdotal evidence and patient testimonies on the Internet are not a sound basis to offer a new treatment "which could have possible procedure-related complications to an often desperate patient population," they wrote. "We believe that until real scientific data are available for CCSVI and balloon dilatation, this treatment should not be offered to MS patients outside of a well designed clinical trial" (Cardiovasc. Intervent. Radiol. 2011;34:1-2).
Toward that end, the National Multiple Sclerosis Society of the United States and the MS Society of Canada have pledged $2.4 million in support of seven CCSVI research studies, including projects designed to evaluate venous abnormalities in children and teens with MS, patients with early and late stage MS, and those at risk for MS. An international review panel comprising radiologists, vascular surgeons, and neurologists evaluated research applications via an expedited review process and chose those that "combined the strongest science with the research goals necessary to most quickly determine the scope and meaning or reported abnormalities in blood drainage from the brain and spinal cord in MS," according to the societies. "It is hoped these findings will provide clarity regarding the need for next-step therapeutic trials to correct such blockages as MS societies around the world pursue this CCSVI lead."
In a presentation at the annual International Symposium of Endovascular Therapy in January, Dr. Burks outlined the critical issues related to crafting a united CCSVI message with multidisciplinary support, which include the best CCSVI diagnostic tests and outcomes; treatment standards and successful outcomes; diagnostic criteria; standards for qualified CCSVI specialists and treatment centers; uniform institutional review board requirements; standards, by discipline, for follow-up care; and criteria for retreatment and procedural standards.
Additionally, "we need to establish a CCSVI patient registry that documents outcomes and adverse events, as well as other relevant data, and disseminate that document widely to all groups," Dr. Burks said. Doing so will go far toward mending the fractious community and directing energy toward optimal patient care, he stated.
Dr. Burks disclosed financial relationships with Acorda, Allergan, Avanir, Bayer, Biogen Idec, Novartis, and Serono. Dr. Baracchini disclosed having no relevant financial relationships.
Multiple sclerosis patients and endovascular interventionalists were elated when Italian researchers reported in 2009 that they had found evidence of chronic cerebrospinal venous insufficiency in nearly every MS patient they had studied and that in many cases, balloon angioplasty and sometimes stent placement of central thoracic veins reduced or eliminated signs of the disease. Neurologists, on the other hand, suggested that hope might be eclipsing reason in the rush to advocate the vascular procedure, given the single-center study’s small sample size and nonrandomized, uncontrolled design.
The opposing perspectives incited an apparent turf war within the MS community fueled by a firestorm of accusations, with both sides going for the jugular, according to Dr. Jack Burks, chief medical officer of the Multiple Sclerosis Association of America. At issue, he said, is the validity not only of the study results but also of the underlying hypothesis that toxic iron overload in the brain due to chronic cerebrospinal venous insufficiency (CCSVI) might have a primary role in the pathogenesis of MS – a hypothesis that contradicts the compelling body of evidence suggesting that MS is primarily an autoimmune condition.
On one side of the debate are the MS patients and endovascular interventionalists, dubbed the "liberators" by Dr. Burks because of their unflappable advocacy for what has become known as the liberation procedure – the endovascular surgery designed to open the lesions causing the venous insufficiency, he said. On the other side are the neurologists and MS societies, whom he lightheartedly calls the CCSVI nihilists because of their outspoken criticism of the surgery in the absence of more robust, conclusive scientific evidence.
"Neurologists believe the interventionalists are overstating the possible value of CCSVI and that commercial interests are overriding scientific inquiry," according to Dr. Burks, a neurologist and clinical professor of medicine at the University of Nevada, Reno. Patients, armed with anecdotal evidence downloaded from the Internet, are certain that CCSVI surgery is the miracle they’ve been waiting for and perceive the hesitancy of U.S. and Canadian neurologists to embrace the treatment as evidence of a possible conspiracy with pharmaceutical companies who stand to lose billions of dollars if the surgery becomes a first-line treatment, he said. Further, he noted, advocates of CCSVI claim that neurologists who refuse patients’ demands for diagnostic testing and surgical referral for CCSVI are jeopardizing the safety of those patients, who are traveling to foreign countries such as Poland, Bulgaria, Mexico, Costa Rica, and India to get the care that they cannot receive in North America.
Both camps point to the much publicized case of a Canadian MS patient who traveled to Costa Rica for jugular vein angioplasty and died from a ruptured vessel as evidence that supports their respective positions, said Dr. Burks.
To date, the majority of the evidence regarding CCSVI diagnosis and treatment in MS is inconsistent, and can be confusing, Dr. Burks noted. In the initial study, Dr. Paolo Zamboni of the University of Ferrara in Italy, and colleagues, used Doppler ultrasound to examine venous drainage of the brain and spinal cord in 65 patients with different types of MS and 235 controls without MS and observed abnormal venous flow in all of the MS patients and none of the controls. The patterns of venous obstruction differed depending on MS stage and course, although there was no apparent relationship between disease severity and extent of venous obstruction, and MS treatment status did not influence the signs of CCSVI in any of the patients, the authors wrote (J. Neurol. Neurosurg. Psychiatry 2009;80:392-9).
The researchers went on to conduct an open pilot study to determine whether percutaneous transluminal angioplasty could safely and effectively treat the narrowing of the extracranial cerebrospinal veins in the 65 MS patients in which the condition was observed – 35 with relapsing-remitting MS, 20 with secondary progressive MS, and 10 with primary progressive MS. They reported significant improvements in MS clinical outcome measures, significant reductions in new brain lesions on MRI, and significant reductions in the number of relapses experienced by some of the patients.
The findings were limited, however, not only by the study design, but also by the fact that patients remained on their disease-modifying antirheumatic drug therapy during the study period and the timing and type of MRI scans varied among the patients, according to the authors. They also noted that restenosis of the internal jugular veins occurred in nearly half of the patients (J. Vasc. Surg. 2009;50:1348-58).
Since the initial paper, a number of CCSVI studies of various designs have been undertaken, with contradictory results. Following are some of the investigations reported within the past year:
• Researchers at the University of Buffalo found that up to 62% of the 280 patients with MS enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation study – the first randomized clinical trial to evaluate MS patients for CCSVI – had the characteristic narrowing of the extracranial veins compared with approximately 22% of 220 healthy controls. While the results, which were reported at the annual meeting of the American Academy of Neurology, did not establish causation, they showed "that narrowing of the extracranial veins, at the very least, is an important association in multiple sclerosis," principal investigator Dr. Robert Zivadinov said in a statement. He acknowledged that the finding of vascular narrowing in nearly a quarter of the healthy controls warranted additional investigation.
• In an open-label study of extracranial Doppler criteria of CCSVI in 70 MS patients in Poland – 49 with relapsing-remitting MS, 5 with primary progressive MS, and 16 with secondary progressive MS – investigators detected at least two of four extracranial criteria in 90% of the patients. They concluded that, while the extracranial abnormalities could exist in various combinations, "the most common pathology in our patients was the presence of an inverted valve or another pathologic structure [like membranaceous or netlike septum] in the area of junction of the [internal jugular vein] with the brachiocephalic vein (Int. Angiol. 2010;29:109-14).
• A comparison of the internal jugular vein hemodynamics and morphology in 25 patients with MS and 25 controls identified abnormal findings in 92% of the MS patients and 24% of the controls, and evidence of CCSVI in 84% of the MS patients and none of the controls, leading the investigators to conclude that both hemodynamic abnormalities and morphologic changes in the internal jugular vein "are strongly associated with MS" (Int. Angiol. 2010;29:115-20).
• An extended extra- and transcranial color-coded sonography study in 56 MS patients and 20 controls detected no internal jugular vein stenosis and normal blood flow direction in all but 1 patient. There were no between-group differences in intracranial veins and during Valsalva maneuver, and none of the patients fulfilled more than one CCSVI criterion, according to the authors. They concluded that their findings "challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS" (Ann. Neurol. 2010;68:173-83).
• Swedish investigators used phase-contrast MRI to study 21 relapsing-remitting MS patients and 20 healthy controls and found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux between the two groups. Although contrast-enhanced MR angiography showed internal jugular vein stenosis in 3 of the 21 MS patients, the authors stated they found no evidence "confirming the suggested vascular multiple sclerosis hypothesis" (Ann. Neurol. 2010;68:255-9).
• The authors of an MR venography and flow quantification study in The Netherlands compared the intracranial and extracranial venous anatomy and the intracerebral venous flow profiles of 20 MS patients and 20 age- and gender-matched controls, with image analysis performed by blinded interventional neuroradiologists. They identified venous system anomalies in 50% of the MS patients and 40% of the healthy controls and no venous backflow in either group. "Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions," the authors wrote (J. Neurol. Neurosurg. Psychiatry 2010 Oct. 27 [doi: 10.1136/jnnp.2010.223479]).
• Italian researchers investigating the occurrence of CCSVI in 50 consecutive patients with clinically isolated syndromes suggestive of MS reviewed the patients’ extracranial and transcranial venous echo-color Doppler sonographs and compared the findings to those of 50 age- and gender matched healthy controls as well as those of 60 patients with transient global amnesia (TGA) and 60 healthy controls matched to the TGA patients. They found extracranial Doppler sonographic abnormalities in 52% of patients with possible MS, 68.3% of patients with TGA, and 31.8% of the healthy controls. While eight of the patients with possible MS fulfilled the CCSVI criteria, selective phlebography showed no venous anomalies in seven of them. The authors concluded that there was no evidence of CCSVI at MS onset but recommended further studies to "clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS" (Ann. Neurol. 2011;69:90-99).
Not only do the findings of this study challenge the hypothesis that CCSVI plays a role in the pathogenesis of MS, they suggest that some patients may be getting unnecessary surgery, according to lead author Dr. Claudio Baracchini of the University of Padua, Italy. "The few patients [in this study] with venous anomalies suggesting a CCSVI pattern had normal cerebral venous hemodynamics and all of the patients who underwent selective venography had predominantly normal findings," he said in an interview. For such patients, the surgery is "unjustified and associated with unnecessary risk," he stressed.
Despite the media focus on the professional divide sparked by the CCSVI controversy, most in the scientific community agree that more research is needed before interventional surgery for CCSVI can be routinely recommended.
In a position statement, the Society of Interventional Radiology stated that at present, the published literature is "inconclusive on whether CCSVI is a clinically important factor in the development and/or progression of MS, and on whether balloon angioplasty and/or stent placement are clinically effective in patients with MS" (J. Vasc. Interv. Radiol. 2010;21:1335-7).
Additionally, in a commentary on the treatment of CCSVI, representatives of the Cardiovascular and Interventional Radiological Society of Europe acknowledged that although several centers worldwide are promoting and performing balloon dilatation, with or without stenting for CCSVI, "no trial data are available, and there is currently no randomized controlled trial [RCT] in progress." Further, anecdotal evidence and patient testimonies on the Internet are not a sound basis to offer a new treatment "which could have possible procedure-related complications to an often desperate patient population," they wrote. "We believe that until real scientific data are available for CCSVI and balloon dilatation, this treatment should not be offered to MS patients outside of a well designed clinical trial" (Cardiovasc. Intervent. Radiol. 2011;34:1-2).
Toward that end, the National Multiple Sclerosis Society of the United States and the MS Society of Canada have pledged $2.4 million in support of seven CCSVI research studies, including projects designed to evaluate venous abnormalities in children and teens with MS, patients with early and late stage MS, and those at risk for MS. An international review panel comprising radiologists, vascular surgeons, and neurologists evaluated research applications via an expedited review process and chose those that "combined the strongest science with the research goals necessary to most quickly determine the scope and meaning or reported abnormalities in blood drainage from the brain and spinal cord in MS," according to the societies. "It is hoped these findings will provide clarity regarding the need for next-step therapeutic trials to correct such blockages as MS societies around the world pursue this CCSVI lead."
In a presentation at the annual International Symposium of Endovascular Therapy in January, Dr. Burks outlined the critical issues related to crafting a united CCSVI message with multidisciplinary support, which include the best CCSVI diagnostic tests and outcomes; treatment standards and successful outcomes; diagnostic criteria; standards for qualified CCSVI specialists and treatment centers; uniform institutional review board requirements; standards, by discipline, for follow-up care; and criteria for retreatment and procedural standards.
Additionally, "we need to establish a CCSVI patient registry that documents outcomes and adverse events, as well as other relevant data, and disseminate that document widely to all groups," Dr. Burks said. Doing so will go far toward mending the fractious community and directing energy toward optimal patient care, he stated.
Dr. Burks disclosed financial relationships with Acorda, Allergan, Avanir, Bayer, Biogen Idec, Novartis, and Serono. Dr. Baracchini disclosed having no relevant financial relationships.
Conflicting CCSVI Data Lead to Call for New Research, United Message
Multiple sclerosis patients and endovascular interventionalists were elated when Italian researchers reported in 2009 that they had found evidence of chronic cerebrospinal venous insufficiency in nearly every MS patient they had studied and that in many cases, balloon angioplasty and sometimes stent placement of central thoracic veins reduced or eliminated signs of the disease. Neurologists, on the other hand, suggested that hope might be eclipsing reason in the rush to advocate the vascular procedure, given the single-center study’s small sample size and nonrandomized, uncontrolled design.
The opposing perspectives incited an apparent turf war within the MS community fueled by a firestorm of accusations, with both sides going for the jugular, according to Dr. Jack Burks, chief medical officer of the Multiple Sclerosis Association of America. At issue, he said, is the validity not only of the study results but also of the underlying hypothesis that toxic iron overload in the brain due to chronic cerebrospinal venous insufficiency (CCSVI) might have a primary role in the pathogenesis of MS – a hypothesis that contradicts the compelling body of evidence suggesting that MS is primarily an autoimmune condition.
On one side of the debate are the MS patients and endovascular interventionalists, dubbed the "liberators" by Dr. Burks because of their unflappable advocacy for what has become known as the liberation procedure – the endovascular surgery designed to open the lesions causing the venous insufficiency, he said. On the other side are the neurologists and MS societies, whom he lightheartedly calls the CCSVI nihilists because of their outspoken criticism of the surgery in the absence of more robust, conclusive scientific evidence.
"Neurologists believe the interventionalists are overstating the possible value of CCSVI and that commercial interests are overriding scientific inquiry," according to Dr. Burks, a neurologist and clinical professor of medicine at the University of Nevada, Reno. Patients, armed with anecdotal evidence downloaded from the Internet, are certain that CCSVI surgery is the miracle they’ve been waiting for and perceive the hesitancy of U.S. and Canadian neurologists to embrace the treatment as evidence of a possible conspiracy with pharmaceutical companies who stand to lose billions of dollars if the surgery becomes a first-line treatment, he said. Further, he noted, advocates of CCSVI claim that neurologists who refuse patients’ demands for diagnostic testing and surgical referral for CCSVI are jeopardizing the safety of those patients, who are traveling to foreign countries such as Poland, Bulgaria, Mexico, Costa Rica, and India to get the care that they cannot receive in North America.
Both camps point to the much publicized case of a Canadian MS patient who traveled to Costa Rica for jugular vein angioplasty and died from a ruptured vessel as evidence that supports their respective positions, said Dr. Burks.
To date, the majority of the evidence regarding CCSVI diagnosis and treatment in MS is inconsistent, and can be confusing, Dr. Burks noted. In the initial study, Dr. Paolo Zamboni of the University of Ferrara in Italy, and colleagues, used Doppler ultrasound to examine venous drainage of the brain and spinal cord in 65 patients with different types of MS and 235 controls without MS and observed abnormal venous flow in all of the MS patients and none of the controls. The patterns of venous obstruction differed depending on MS stage and course, although there was no apparent relationship between disease severity and extent of venous obstruction, and MS treatment status did not influence the signs of CCSVI in any of the patients, the authors wrote (J. Neurol. Neurosurg. Psychiatry 2009;80:392-9).
The researchers went on to conduct an open pilot study to determine whether percutaneous transluminal angioplasty could safely and effectively treat the narrowing of the extracranial cerebrospinal veins in the 65 MS patients in which the condition was observed – 35 with relapsing-remitting MS, 20 with secondary progressive MS, and 10 with primary progressive MS. They reported significant improvements in MS clinical outcome measures, significant reductions in new brain lesions on MRI, and significant reductions in the number of relapses experienced by some of the patients.
The findings were limited, however, not only by the study design, but also by the fact that patients remained on their disease-modifying antirheumatic drug therapy during the study period and the timing and type of MRI scans varied among the patients, according to the authors. They also noted that restenosis of the internal jugular veins occurred in nearly half of the patients (J. Vasc. Surg. 2009;50:1348-58).
Since the initial paper, a number of CCSVI studies of various designs have been undertaken, with contradictory results. Following are some of the investigations reported within the past year:
• Researchers at the University of Buffalo found that up to 62% of the 280 patients with MS enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation study – the first randomized clinical trial to evaluate MS patients for CCSVI – had the characteristic narrowing of the extracranial veins compared with approximately 22% of 220 healthy controls. While the results, which were reported at the annual meeting of the American Academy of Neurology, did not establish causation, they showed "that narrowing of the extracranial veins, at the very least, is an important association in multiple sclerosis," principal investigator Dr. Robert Zivadinov said in a statement. He acknowledged that the finding of vascular narrowing in nearly a quarter of the healthy controls warranted additional investigation.
• In an open-label study of extracranial Doppler criteria of CCSVI in 70 MS patients in Poland – 49 with relapsing-remitting MS, 5 with primary progressive MS, and 16 with secondary progressive MS – investigators detected at least two of four extracranial criteria in 90% of the patients. They concluded that, while the extracranial abnormalities could exist in various combinations, "the most common pathology in our patients was the presence of an inverted valve or another pathologic structure [like membranaceous or netlike septum] in the area of junction of the [internal jugular vein] with the brachiocephalic vein (Int. Angiol. 2010;29:109-14).
• A comparison of the internal jugular vein hemodynamics and morphology in 25 patients with MS and 25 controls identified abnormal findings in 92% of the MS patients and 24% of the controls, and evidence of CCSVI in 84% of the MS patients and none of the controls, leading the investigators to conclude that both hemodynamic abnormalities and morphologic changes in the internal jugular vein "are strongly associated with MS" (Int. Angiol. 2010;29:115-20).
• An extended extra- and transcranial color-coded sonography study in 56 MS patients and 20 controls detected no internal jugular vein stenosis and normal blood flow direction in all but 1 patient. There were no between-group differences in intracranial veins and during Valsalva maneuver, and none of the patients fulfilled more than one CCSVI criterion, according to the authors. They concluded that their findings "challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS" (Ann. Neurol. 2010;68:173-83).
• Swedish investigators used phase-contrast MRI to study 21 relapsing-remitting MS patients and 20 healthy controls and found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux between the two groups. Although contrast-enhanced MR angiography showed internal jugular vein stenosis in 3 of the 21 MS patients, the authors stated they found no evidence "confirming the suggested vascular multiple sclerosis hypothesis" (Ann. Neurol. 2010;68:255-9).
• The authors of an MR venography and flow quantification study in The Netherlands compared the intracranial and extracranial venous anatomy and the intracerebral venous flow profiles of 20 MS patients and 20 age- and gender-matched controls, with image analysis performed by blinded interventional neuroradiologists. They identified venous system anomalies in 50% of the MS patients and 40% of the healthy controls and no venous backflow in either group. "Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions," the authors wrote (J. Neurol. Neurosurg. Psychiatry 2010 Oct. 27 [doi: 10.1136/jnnp.2010.223479]).
• Italian researchers investigating the occurrence of CCSVI in 50 consecutive patients with clinically isolated syndromes suggestive of MS reviewed the patients’ extracranial and transcranial venous echo-color Doppler sonographs and compared the findings to those of 50 age- and gender matched healthy controls as well as those of 60 patients with transient global amnesia (TGA) and 60 healthy controls matched to the TGA patients. They found extracranial Doppler sonographic abnormalities in 52% of patients with possible MS, 68.3% of patients with TGA, and 31.8% of the healthy controls. While eight of the patients with possible MS fulfilled the CCSVI criteria, selective phlebography showed no venous anomalies in seven of them. The authors concluded that there was no evidence of CCSVI at MS onset but recommended further studies to "clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS" (Ann. Neurol. 2011;69:90-99).
Not only do the findings of this study challenge the hypothesis that CCSVI plays a role in the pathogenesis of MS, they suggest that some patients may be getting unnecessary surgery, according to lead author Dr. Claudio Baracchini of the University of Padua, Italy. "The few patients [in this study] with venous anomalies suggesting a CCSVI pattern had normal cerebral venous hemodynamics and all of the patients who underwent selective venography had predominantly normal findings," he said in an interview. For such patients, the surgery is "unjustified and associated with unnecessary risk," he stressed.
Despite the media focus on the professional divide sparked by the CCSVI controversy, most in the scientific community agree that more research is needed before interventional surgery for CCSVI can be routinely recommended.
In a position statement, the Society of Interventional Radiology stated that at present, the published literature is "inconclusive on whether CCSVI is a clinically important factor in the development and/or progression of MS, and on whether balloon angioplasty and/or stent placement are clinically effective in patients with MS" (J. Vasc. Interv. Radiol. 2010;21:1335-7).
Additionally, in a commentary on the treatment of CCSVI, representatives of the Cardiovascular and Interventional Radiological Society of Europe acknowledged that although several centers worldwide are promoting and performing balloon dilatation, with or without stenting for CCSVI, "no trial data are available, and there is currently no randomized controlled trial [RCT] in progress." Further, anecdotal evidence and patient testimonies on the Internet are not a sound basis to offer a new treatment "which could have possible procedure-related complications to an often desperate patient population," they wrote. "We believe that until real scientific data are available for CCSVI and balloon dilatation, this treatment should not be offered to MS patients outside of a well designed clinical trial" (Cardiovasc. Intervent. Radiol. 2011;34:1-2).
Toward that end, the National Multiple Sclerosis Society of the United States and the MS Society of Canada have pledged $2.4 million in support of seven CCSVI research studies, including projects designed to evaluate venous abnormalities in children and teens with MS, patients with early and late stage MS, and those at risk for MS. An international review panel comprising radiologists, vascular surgeons, and neurologists evaluated research applications via an expedited review process and chose those that "combined the strongest science with the research goals necessary to most quickly determine the scope and meaning or reported abnormalities in blood drainage from the brain and spinal cord in MS," according to the societies. "It is hoped these findings will provide clarity regarding the need for next-step therapeutic trials to correct such blockages as MS societies around the world pursue this CCSVI lead."
In a presentation at the annual International Symposium of Endovascular Therapy in January, Dr. Burks outlined the critical issues related to crafting a united CCSVI message with multidisciplinary support, which include the best CCSVI diagnostic tests and outcomes; treatment standards and successful outcomes; diagnostic criteria; standards for qualified CCSVI specialists and treatment centers; uniform institutional review board requirements; standards, by discipline, for follow-up care; and criteria for retreatment and procedural standards.
Additionally, "we need to establish a CCSVI patient registry that documents outcomes and adverse events, as well as other relevant data, and disseminate that document widely to all groups," Dr. Burks said. Doing so will go far toward mending the fractious community and directing energy toward optimal patient care, he stated.
Dr. Burks disclosed financial relationships with Acorda, Allergan, Avanir, Bayer, Biogen Idec, Novartis, and Serono. Dr. Baracchini disclosed having no relevant financial relationships.
Multiple sclerosis patients and endovascular interventionalists were elated when Italian researchers reported in 2009 that they had found evidence of chronic cerebrospinal venous insufficiency in nearly every MS patient they had studied and that in many cases, balloon angioplasty and sometimes stent placement of central thoracic veins reduced or eliminated signs of the disease. Neurologists, on the other hand, suggested that hope might be eclipsing reason in the rush to advocate the vascular procedure, given the single-center study’s small sample size and nonrandomized, uncontrolled design.
The opposing perspectives incited an apparent turf war within the MS community fueled by a firestorm of accusations, with both sides going for the jugular, according to Dr. Jack Burks, chief medical officer of the Multiple Sclerosis Association of America. At issue, he said, is the validity not only of the study results but also of the underlying hypothesis that toxic iron overload in the brain due to chronic cerebrospinal venous insufficiency (CCSVI) might have a primary role in the pathogenesis of MS – a hypothesis that contradicts the compelling body of evidence suggesting that MS is primarily an autoimmune condition.
On one side of the debate are the MS patients and endovascular interventionalists, dubbed the "liberators" by Dr. Burks because of their unflappable advocacy for what has become known as the liberation procedure – the endovascular surgery designed to open the lesions causing the venous insufficiency, he said. On the other side are the neurologists and MS societies, whom he lightheartedly calls the CCSVI nihilists because of their outspoken criticism of the surgery in the absence of more robust, conclusive scientific evidence.
"Neurologists believe the interventionalists are overstating the possible value of CCSVI and that commercial interests are overriding scientific inquiry," according to Dr. Burks, a neurologist and clinical professor of medicine at the University of Nevada, Reno. Patients, armed with anecdotal evidence downloaded from the Internet, are certain that CCSVI surgery is the miracle they’ve been waiting for and perceive the hesitancy of U.S. and Canadian neurologists to embrace the treatment as evidence of a possible conspiracy with pharmaceutical companies who stand to lose billions of dollars if the surgery becomes a first-line treatment, he said. Further, he noted, advocates of CCSVI claim that neurologists who refuse patients’ demands for diagnostic testing and surgical referral for CCSVI are jeopardizing the safety of those patients, who are traveling to foreign countries such as Poland, Bulgaria, Mexico, Costa Rica, and India to get the care that they cannot receive in North America.
Both camps point to the much publicized case of a Canadian MS patient who traveled to Costa Rica for jugular vein angioplasty and died from a ruptured vessel as evidence that supports their respective positions, said Dr. Burks.
To date, the majority of the evidence regarding CCSVI diagnosis and treatment in MS is inconsistent, and can be confusing, Dr. Burks noted. In the initial study, Dr. Paolo Zamboni of the University of Ferrara in Italy, and colleagues, used Doppler ultrasound to examine venous drainage of the brain and spinal cord in 65 patients with different types of MS and 235 controls without MS and observed abnormal venous flow in all of the MS patients and none of the controls. The patterns of venous obstruction differed depending on MS stage and course, although there was no apparent relationship between disease severity and extent of venous obstruction, and MS treatment status did not influence the signs of CCSVI in any of the patients, the authors wrote (J. Neurol. Neurosurg. Psychiatry 2009;80:392-9).
The researchers went on to conduct an open pilot study to determine whether percutaneous transluminal angioplasty could safely and effectively treat the narrowing of the extracranial cerebrospinal veins in the 65 MS patients in which the condition was observed – 35 with relapsing-remitting MS, 20 with secondary progressive MS, and 10 with primary progressive MS. They reported significant improvements in MS clinical outcome measures, significant reductions in new brain lesions on MRI, and significant reductions in the number of relapses experienced by some of the patients.
The findings were limited, however, not only by the study design, but also by the fact that patients remained on their disease-modifying antirheumatic drug therapy during the study period and the timing and type of MRI scans varied among the patients, according to the authors. They also noted that restenosis of the internal jugular veins occurred in nearly half of the patients (J. Vasc. Surg. 2009;50:1348-58).
Since the initial paper, a number of CCSVI studies of various designs have been undertaken, with contradictory results. Following are some of the investigations reported within the past year:
• Researchers at the University of Buffalo found that up to 62% of the 280 patients with MS enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation study – the first randomized clinical trial to evaluate MS patients for CCSVI – had the characteristic narrowing of the extracranial veins compared with approximately 22% of 220 healthy controls. While the results, which were reported at the annual meeting of the American Academy of Neurology, did not establish causation, they showed "that narrowing of the extracranial veins, at the very least, is an important association in multiple sclerosis," principal investigator Dr. Robert Zivadinov said in a statement. He acknowledged that the finding of vascular narrowing in nearly a quarter of the healthy controls warranted additional investigation.
• In an open-label study of extracranial Doppler criteria of CCSVI in 70 MS patients in Poland – 49 with relapsing-remitting MS, 5 with primary progressive MS, and 16 with secondary progressive MS – investigators detected at least two of four extracranial criteria in 90% of the patients. They concluded that, while the extracranial abnormalities could exist in various combinations, "the most common pathology in our patients was the presence of an inverted valve or another pathologic structure [like membranaceous or netlike septum] in the area of junction of the [internal jugular vein] with the brachiocephalic vein (Int. Angiol. 2010;29:109-14).
• A comparison of the internal jugular vein hemodynamics and morphology in 25 patients with MS and 25 controls identified abnormal findings in 92% of the MS patients and 24% of the controls, and evidence of CCSVI in 84% of the MS patients and none of the controls, leading the investigators to conclude that both hemodynamic abnormalities and morphologic changes in the internal jugular vein "are strongly associated with MS" (Int. Angiol. 2010;29:115-20).
• An extended extra- and transcranial color-coded sonography study in 56 MS patients and 20 controls detected no internal jugular vein stenosis and normal blood flow direction in all but 1 patient. There were no between-group differences in intracranial veins and during Valsalva maneuver, and none of the patients fulfilled more than one CCSVI criterion, according to the authors. They concluded that their findings "challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS" (Ann. Neurol. 2010;68:173-83).
• Swedish investigators used phase-contrast MRI to study 21 relapsing-remitting MS patients and 20 healthy controls and found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux between the two groups. Although contrast-enhanced MR angiography showed internal jugular vein stenosis in 3 of the 21 MS patients, the authors stated they found no evidence "confirming the suggested vascular multiple sclerosis hypothesis" (Ann. Neurol. 2010;68:255-9).
• The authors of an MR venography and flow quantification study in The Netherlands compared the intracranial and extracranial venous anatomy and the intracerebral venous flow profiles of 20 MS patients and 20 age- and gender-matched controls, with image analysis performed by blinded interventional neuroradiologists. They identified venous system anomalies in 50% of the MS patients and 40% of the healthy controls and no venous backflow in either group. "Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions," the authors wrote (J. Neurol. Neurosurg. Psychiatry 2010 Oct. 27 [doi: 10.1136/jnnp.2010.223479]).
• Italian researchers investigating the occurrence of CCSVI in 50 consecutive patients with clinically isolated syndromes suggestive of MS reviewed the patients’ extracranial and transcranial venous echo-color Doppler sonographs and compared the findings to those of 50 age- and gender matched healthy controls as well as those of 60 patients with transient global amnesia (TGA) and 60 healthy controls matched to the TGA patients. They found extracranial Doppler sonographic abnormalities in 52% of patients with possible MS, 68.3% of patients with TGA, and 31.8% of the healthy controls. While eight of the patients with possible MS fulfilled the CCSVI criteria, selective phlebography showed no venous anomalies in seven of them. The authors concluded that there was no evidence of CCSVI at MS onset but recommended further studies to "clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS" (Ann. Neurol. 2011;69:90-99).
Not only do the findings of this study challenge the hypothesis that CCSVI plays a role in the pathogenesis of MS, they suggest that some patients may be getting unnecessary surgery, according to lead author Dr. Claudio Baracchini of the University of Padua, Italy. "The few patients [in this study] with venous anomalies suggesting a CCSVI pattern had normal cerebral venous hemodynamics and all of the patients who underwent selective venography had predominantly normal findings," he said in an interview. For such patients, the surgery is "unjustified and associated with unnecessary risk," he stressed.
Despite the media focus on the professional divide sparked by the CCSVI controversy, most in the scientific community agree that more research is needed before interventional surgery for CCSVI can be routinely recommended.
In a position statement, the Society of Interventional Radiology stated that at present, the published literature is "inconclusive on whether CCSVI is a clinically important factor in the development and/or progression of MS, and on whether balloon angioplasty and/or stent placement are clinically effective in patients with MS" (J. Vasc. Interv. Radiol. 2010;21:1335-7).
Additionally, in a commentary on the treatment of CCSVI, representatives of the Cardiovascular and Interventional Radiological Society of Europe acknowledged that although several centers worldwide are promoting and performing balloon dilatation, with or without stenting for CCSVI, "no trial data are available, and there is currently no randomized controlled trial [RCT] in progress." Further, anecdotal evidence and patient testimonies on the Internet are not a sound basis to offer a new treatment "which could have possible procedure-related complications to an often desperate patient population," they wrote. "We believe that until real scientific data are available for CCSVI and balloon dilatation, this treatment should not be offered to MS patients outside of a well designed clinical trial" (Cardiovasc. Intervent. Radiol. 2011;34:1-2).
Toward that end, the National Multiple Sclerosis Society of the United States and the MS Society of Canada have pledged $2.4 million in support of seven CCSVI research studies, including projects designed to evaluate venous abnormalities in children and teens with MS, patients with early and late stage MS, and those at risk for MS. An international review panel comprising radiologists, vascular surgeons, and neurologists evaluated research applications via an expedited review process and chose those that "combined the strongest science with the research goals necessary to most quickly determine the scope and meaning or reported abnormalities in blood drainage from the brain and spinal cord in MS," according to the societies. "It is hoped these findings will provide clarity regarding the need for next-step therapeutic trials to correct such blockages as MS societies around the world pursue this CCSVI lead."
In a presentation at the annual International Symposium of Endovascular Therapy in January, Dr. Burks outlined the critical issues related to crafting a united CCSVI message with multidisciplinary support, which include the best CCSVI diagnostic tests and outcomes; treatment standards and successful outcomes; diagnostic criteria; standards for qualified CCSVI specialists and treatment centers; uniform institutional review board requirements; standards, by discipline, for follow-up care; and criteria for retreatment and procedural standards.
Additionally, "we need to establish a CCSVI patient registry that documents outcomes and adverse events, as well as other relevant data, and disseminate that document widely to all groups," Dr. Burks said. Doing so will go far toward mending the fractious community and directing energy toward optimal patient care, he stated.
Dr. Burks disclosed financial relationships with Acorda, Allergan, Avanir, Bayer, Biogen Idec, Novartis, and Serono. Dr. Baracchini disclosed having no relevant financial relationships.
Multiple sclerosis patients and endovascular interventionalists were elated when Italian researchers reported in 2009 that they had found evidence of chronic cerebrospinal venous insufficiency in nearly every MS patient they had studied and that in many cases, balloon angioplasty and sometimes stent placement of central thoracic veins reduced or eliminated signs of the disease. Neurologists, on the other hand, suggested that hope might be eclipsing reason in the rush to advocate the vascular procedure, given the single-center study’s small sample size and nonrandomized, uncontrolled design.
The opposing perspectives incited an apparent turf war within the MS community fueled by a firestorm of accusations, with both sides going for the jugular, according to Dr. Jack Burks, chief medical officer of the Multiple Sclerosis Association of America. At issue, he said, is the validity not only of the study results but also of the underlying hypothesis that toxic iron overload in the brain due to chronic cerebrospinal venous insufficiency (CCSVI) might have a primary role in the pathogenesis of MS – a hypothesis that contradicts the compelling body of evidence suggesting that MS is primarily an autoimmune condition.
On one side of the debate are the MS patients and endovascular interventionalists, dubbed the "liberators" by Dr. Burks because of their unflappable advocacy for what has become known as the liberation procedure – the endovascular surgery designed to open the lesions causing the venous insufficiency, he said. On the other side are the neurologists and MS societies, whom he lightheartedly calls the CCSVI nihilists because of their outspoken criticism of the surgery in the absence of more robust, conclusive scientific evidence.
"Neurologists believe the interventionalists are overstating the possible value of CCSVI and that commercial interests are overriding scientific inquiry," according to Dr. Burks, a neurologist and clinical professor of medicine at the University of Nevada, Reno. Patients, armed with anecdotal evidence downloaded from the Internet, are certain that CCSVI surgery is the miracle they’ve been waiting for and perceive the hesitancy of U.S. and Canadian neurologists to embrace the treatment as evidence of a possible conspiracy with pharmaceutical companies who stand to lose billions of dollars if the surgery becomes a first-line treatment, he said. Further, he noted, advocates of CCSVI claim that neurologists who refuse patients’ demands for diagnostic testing and surgical referral for CCSVI are jeopardizing the safety of those patients, who are traveling to foreign countries such as Poland, Bulgaria, Mexico, Costa Rica, and India to get the care that they cannot receive in North America.
Both camps point to the much publicized case of a Canadian MS patient who traveled to Costa Rica for jugular vein angioplasty and died from a ruptured vessel as evidence that supports their respective positions, said Dr. Burks.
To date, the majority of the evidence regarding CCSVI diagnosis and treatment in MS is inconsistent, and can be confusing, Dr. Burks noted. In the initial study, Dr. Paolo Zamboni of the University of Ferrara in Italy, and colleagues, used Doppler ultrasound to examine venous drainage of the brain and spinal cord in 65 patients with different types of MS and 235 controls without MS and observed abnormal venous flow in all of the MS patients and none of the controls. The patterns of venous obstruction differed depending on MS stage and course, although there was no apparent relationship between disease severity and extent of venous obstruction, and MS treatment status did not influence the signs of CCSVI in any of the patients, the authors wrote (J. Neurol. Neurosurg. Psychiatry 2009;80:392-9).
The researchers went on to conduct an open pilot study to determine whether percutaneous transluminal angioplasty could safely and effectively treat the narrowing of the extracranial cerebrospinal veins in the 65 MS patients in which the condition was observed – 35 with relapsing-remitting MS, 20 with secondary progressive MS, and 10 with primary progressive MS. They reported significant improvements in MS clinical outcome measures, significant reductions in new brain lesions on MRI, and significant reductions in the number of relapses experienced by some of the patients.
The findings were limited, however, not only by the study design, but also by the fact that patients remained on their disease-modifying antirheumatic drug therapy during the study period and the timing and type of MRI scans varied among the patients, according to the authors. They also noted that restenosis of the internal jugular veins occurred in nearly half of the patients (J. Vasc. Surg. 2009;50:1348-58).
Since the initial paper, a number of CCSVI studies of various designs have been undertaken, with contradictory results. Following are some of the investigations reported within the past year:
• Researchers at the University of Buffalo found that up to 62% of the 280 patients with MS enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation study – the first randomized clinical trial to evaluate MS patients for CCSVI – had the characteristic narrowing of the extracranial veins compared with approximately 22% of 220 healthy controls. While the results, which were reported at the annual meeting of the American Academy of Neurology, did not establish causation, they showed "that narrowing of the extracranial veins, at the very least, is an important association in multiple sclerosis," principal investigator Dr. Robert Zivadinov said in a statement. He acknowledged that the finding of vascular narrowing in nearly a quarter of the healthy controls warranted additional investigation.
• In an open-label study of extracranial Doppler criteria of CCSVI in 70 MS patients in Poland – 49 with relapsing-remitting MS, 5 with primary progressive MS, and 16 with secondary progressive MS – investigators detected at least two of four extracranial criteria in 90% of the patients. They concluded that, while the extracranial abnormalities could exist in various combinations, "the most common pathology in our patients was the presence of an inverted valve or another pathologic structure [like membranaceous or netlike septum] in the area of junction of the [internal jugular vein] with the brachiocephalic vein (Int. Angiol. 2010;29:109-14).
• A comparison of the internal jugular vein hemodynamics and morphology in 25 patients with MS and 25 controls identified abnormal findings in 92% of the MS patients and 24% of the controls, and evidence of CCSVI in 84% of the MS patients and none of the controls, leading the investigators to conclude that both hemodynamic abnormalities and morphologic changes in the internal jugular vein "are strongly associated with MS" (Int. Angiol. 2010;29:115-20).
• An extended extra- and transcranial color-coded sonography study in 56 MS patients and 20 controls detected no internal jugular vein stenosis and normal blood flow direction in all but 1 patient. There were no between-group differences in intracranial veins and during Valsalva maneuver, and none of the patients fulfilled more than one CCSVI criterion, according to the authors. They concluded that their findings "challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS" (Ann. Neurol. 2010;68:173-83).
• Swedish investigators used phase-contrast MRI to study 21 relapsing-remitting MS patients and 20 healthy controls and found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux between the two groups. Although contrast-enhanced MR angiography showed internal jugular vein stenosis in 3 of the 21 MS patients, the authors stated they found no evidence "confirming the suggested vascular multiple sclerosis hypothesis" (Ann. Neurol. 2010;68:255-9).
• The authors of an MR venography and flow quantification study in The Netherlands compared the intracranial and extracranial venous anatomy and the intracerebral venous flow profiles of 20 MS patients and 20 age- and gender-matched controls, with image analysis performed by blinded interventional neuroradiologists. They identified venous system anomalies in 50% of the MS patients and 40% of the healthy controls and no venous backflow in either group. "Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions," the authors wrote (J. Neurol. Neurosurg. Psychiatry 2010 Oct. 27 [doi: 10.1136/jnnp.2010.223479]).
• Italian researchers investigating the occurrence of CCSVI in 50 consecutive patients with clinically isolated syndromes suggestive of MS reviewed the patients’ extracranial and transcranial venous echo-color Doppler sonographs and compared the findings to those of 50 age- and gender matched healthy controls as well as those of 60 patients with transient global amnesia (TGA) and 60 healthy controls matched to the TGA patients. They found extracranial Doppler sonographic abnormalities in 52% of patients with possible MS, 68.3% of patients with TGA, and 31.8% of the healthy controls. While eight of the patients with possible MS fulfilled the CCSVI criteria, selective phlebography showed no venous anomalies in seven of them. The authors concluded that there was no evidence of CCSVI at MS onset but recommended further studies to "clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS" (Ann. Neurol. 2011;69:90-99).
Not only do the findings of this study challenge the hypothesis that CCSVI plays a role in the pathogenesis of MS, they suggest that some patients may be getting unnecessary surgery, according to lead author Dr. Claudio Baracchini of the University of Padua, Italy. "The few patients [in this study] with venous anomalies suggesting a CCSVI pattern had normal cerebral venous hemodynamics and all of the patients who underwent selective venography had predominantly normal findings," he said in an interview. For such patients, the surgery is "unjustified and associated with unnecessary risk," he stressed.
Despite the media focus on the professional divide sparked by the CCSVI controversy, most in the scientific community agree that more research is needed before interventional surgery for CCSVI can be routinely recommended.
In a position statement, the Society of Interventional Radiology stated that at present, the published literature is "inconclusive on whether CCSVI is a clinically important factor in the development and/or progression of MS, and on whether balloon angioplasty and/or stent placement are clinically effective in patients with MS" (J. Vasc. Interv. Radiol. 2010;21:1335-7).
Additionally, in a commentary on the treatment of CCSVI, representatives of the Cardiovascular and Interventional Radiological Society of Europe acknowledged that although several centers worldwide are promoting and performing balloon dilatation, with or without stenting for CCSVI, "no trial data are available, and there is currently no randomized controlled trial [RCT] in progress." Further, anecdotal evidence and patient testimonies on the Internet are not a sound basis to offer a new treatment "which could have possible procedure-related complications to an often desperate patient population," they wrote. "We believe that until real scientific data are available for CCSVI and balloon dilatation, this treatment should not be offered to MS patients outside of a well designed clinical trial" (Cardiovasc. Intervent. Radiol. 2011;34:1-2).
Toward that end, the National Multiple Sclerosis Society of the United States and the MS Society of Canada have pledged $2.4 million in support of seven CCSVI research studies, including projects designed to evaluate venous abnormalities in children and teens with MS, patients with early and late stage MS, and those at risk for MS. An international review panel comprising radiologists, vascular surgeons, and neurologists evaluated research applications via an expedited review process and chose those that "combined the strongest science with the research goals necessary to most quickly determine the scope and meaning or reported abnormalities in blood drainage from the brain and spinal cord in MS," according to the societies. "It is hoped these findings will provide clarity regarding the need for next-step therapeutic trials to correct such blockages as MS societies around the world pursue this CCSVI lead."
In a presentation at the annual International Symposium of Endovascular Therapy in January, Dr. Burks outlined the critical issues related to crafting a united CCSVI message with multidisciplinary support, which include the best CCSVI diagnostic tests and outcomes; treatment standards and successful outcomes; diagnostic criteria; standards for qualified CCSVI specialists and treatment centers; uniform institutional review board requirements; standards, by discipline, for follow-up care; and criteria for retreatment and procedural standards.
Additionally, "we need to establish a CCSVI patient registry that documents outcomes and adverse events, as well as other relevant data, and disseminate that document widely to all groups," Dr. Burks said. Doing so will go far toward mending the fractious community and directing energy toward optimal patient care, he stated.
Dr. Burks disclosed financial relationships with Acorda, Allergan, Avanir, Bayer, Biogen Idec, Novartis, and Serono. Dr. Baracchini disclosed having no relevant financial relationships.
DIAMOND Is Gem for Depression Care
A depression care model aiming to bridge the gap between what is known about mental health obstacles and what is being done to minimize them has led to the successful communion of science and practice across Minnesota.
The model, called Depression Improvement Across Minnesota Offering a New Direction, or DIAMOND, uses a team-based approach to facilitate the screening, diagnosis, and management of depression among patients in 83 primary care practices across the state.
The DIAMOND approach, in which the care of patients who screen positive for depression in the primary care setting is choreographed by care managers and overseen by consulting psychiatrists, is not a novel one. In fact, a well-established body of evidence indicates that team care models improve outcomes in depression and reduce health care use costs over time (J. Occup. Environ. Med. 2008;50:459-67).
The unique aspect of the DIAMOND model is that it is the first depression treatment program in the country to integrate the team-based paradigm with a reimbursement structure that supports the provision of enhanced mental health care support in primary care clinics, according to Dr. Brian Rank. Dr. Rank is medical director of HealthPartners Medical Group in Minneapolis and chair of the board of directors for the Institute for Clinical Systems Improvement (ICSI) in Bloomington, Minn. ICSI is a nonprofit group that spearheaded the development and launch of DIAMOND in 2008 in collaboration with more than 60 medical groups, hospitals, and health plans.
Specifically, each medical group participating in DIAMOND receives a monthly fee for every enrolled patient, said Dr. Mark D. Williams of the Mayo Clinic in Rochester, Minn. The fee, predetermined through collaboration with the state’s major insurers and represented by a single, specific billing code, covers the care "bundle," which includes depression screening and monitoring using the Patient Health Questionnaire (PHQ-9); weekly psychiatric consultation and case review; ongoing contact with the care manager; communication between the care manager, psychiatrist, and primary care physician; relapse prevention visits; and use of a patient registry.
"The fee addresses one of the main questions challenging health care improvement in this country: Who is going to pay for it?" Dr. Williams said in an interview. "The way health care is designed in the United States, practices are trying to manage lots of patients, because the only way they can survive is through volume. So, when you suggest trying a different model – one that requires hiring a resource care manager or pulling someone out of a different position from a busy clinic – the practices see risk. Their margins are so small already, committing to the change, even if it is evidence based, is difficult."
Because of the financial realities, the DIAMOND team had to figure out a way to implement the program in practices without the shadow of financial disincentives. "The challenge wasn’t proving it would work – there are lots of randomized controlled trials supporting the collaborative care model – the challenge was showing the practices that the costs wouldn’t be overwhelming," Dr. Williams said. "The promise of new income through the monthly fee was something that allowed the practices to go to their boards and argue that the new model would improve patient management without putting the practice at risk."
The DIAMOND protocol is built around the main elements of the Improving Mood: Promoting Access to Collaborative Treatment (IMPACT) program developed by Dr. Jürgen Unützer of the University of Washington (http://impact-uw.org/). These elements include:
• Standard and reliable use of the PHQ-9 for assessment and ongoing depression management;
• Use of an evidence-based guideline and a stepped-care approach for treatment modification or intensification;
• Development and use of a registry to monitor and track patients;
• Relapse-prevention training for patients reaching remission;
• Introduction of a trained care manager; and
• A formal relationship with a consulting psychiatrist.
The DIAMOND implementation differs from IMPACT, in that the DIAMOND care managers do not have to be nurses with psychiatric experience, according to Nancy Jaeckels, vice president of member relations and strategic initiatives for ICSI. Rather, DIAMOND has hired and trained various health care personnel to serve as care managers, including medical assistants, social workers, and licensed practical nurses, she said.
In participating practices, patients aged 18 years or older with a primary care diagnosis of major depression or dysthymia and a PHQ-9 score of at least 10 are enrolled in the DIAMOND program.
The care protocol includes an initial review of PHQ-9 results and symptoms with the primary care physician; an intake meeting with the care manager, during which patients are screened for other mental health or substance use problems; and weekly phone or in-person follow-up contact with the care manager to discuss treatment status and to complete the PHQ-9, the results of which the care manager enters into the patient registry, along with information on the patient’s medication, treatment adjustments, and behavior.
The DIAMOND protocol also includes a weekly meeting between the consulting psychiatrist and the care manager to review care and discuss patient-related issues or concerns; and periodic direct contact between the psychiatrist and the primary care provider, who is the medication prescriber, to assess treatment response and make adjustments as necessary.
"In some instances, there are patients who need more than DIAMOND can offer, so we spend a fair amount of energy linking with local mental health resources, advocating for the patients as much as possible," Dr. Williams said.
Patients enrolled in DIAMOND are covered for a maximum of 12 consecutive months, Ms. Jaeckels said. Before moving out of care management, they complete a relapse prevention plan with their care manager that includes an action plan if symptoms recur, she said.
The DIAMOND model addresses important deficiencies in the current management of depression in primary care, Dr. Williams said. "Even though we have outcome measures to tell when someone [with depression] is in trouble or improving, a lot of times primary care physicians don’t use these and instead ask questions like, ‘How is it going?’ or ‘How is the depression?’ That’s kind of like asking a patient with hypertension how he or she is doing without measuring blood pressure. It doesn’t make sense."
Another obstacle in traditional settings is that patients with depression "typically are not activated," Dr. Williams said. "They have trouble getting going and doing things, and they commonly feel overwhelmed by the fragmentation of the health care system, the difficulty getting appointments, problems with their prescriptions, to the point where they just stop doing what they should be doing and things get really bad," he explained. "This is where the care managers are so important, because they reach out to the patients, maintain the connection, and help them navigate."
The effort appears to be worth it, according to a review of primary outcome data from March 2008 through March 2010 reported on the public Minnesota Health Scores Web site. The site reported 6-month depression remission rates between 7% and 51%, compared with rates between 0% and 10% in clinics not using DIAMOND. An additional 16% of the DIAMOND patients experienced at least a 50% reduction in depression symptom severity – a rate nearly 10 times higher than that observed in the usual-care patients (www.mnhealthscores.org).
In addition to addressing symptoms of depression, the program leads to improvements in other areas, Dr. Williams said. "When patients are depressed, they tend not to deal with their other issues, such as asthma, diabetes, and alcohol abuse. As their symptoms improve and through the care collaboration, we start to identify some of those issues." This is one reason that, on paper, the health care costs during the first year of the program occasionally increase, he said.
"After some of these issues are addressed, the health care utilization costs actually drop substantially per patient, but that can take 3-4 years, and insurance companies are interested in the fiscal year."
Financial considerations, although addressed on the front end through the bundled fee, might ultimately present the biggest challenge to DIAMOND’s survival, Dr. Williams stated.
"Medicare and Medicaid have not yet agreed that this is worth paying for, despite having evidence that it works better than usual care and that the initial costs are likely to be offset quickly." This is because "there is a lot of pressure on them with universal health care to talk about the health care home," he said. "There’s a lot of uncertainty about whether the health care home is going to be a reality, so there is a hesitation to commit to other collaborative models."
In reality, the DIAMOND program, with its sustainable payment model, could be an important building block for the health care home, Dr. Williams stressed. In a recent case study evaluating the DIAMOND effort, he and his colleagues concluded that the model "offers a new direction" for achieving the goal of creating value in depression management, particularly at the mental health and primary care interface (Qual. Prim. Care 2010;18:327-33).
Dr. Williams and Dr. Rank have no relevant financial disclosures.
A depression care model aiming to bridge the gap between what is known about mental health obstacles and what is being done to minimize them has led to the successful communion of science and practice across Minnesota.
The model, called Depression Improvement Across Minnesota Offering a New Direction, or DIAMOND, uses a team-based approach to facilitate the screening, diagnosis, and management of depression among patients in 83 primary care practices across the state.
The DIAMOND approach, in which the care of patients who screen positive for depression in the primary care setting is choreographed by care managers and overseen by consulting psychiatrists, is not a novel one. In fact, a well-established body of evidence indicates that team care models improve outcomes in depression and reduce health care use costs over time (J. Occup. Environ. Med. 2008;50:459-67).
The unique aspect of the DIAMOND model is that it is the first depression treatment program in the country to integrate the team-based paradigm with a reimbursement structure that supports the provision of enhanced mental health care support in primary care clinics, according to Dr. Brian Rank. Dr. Rank is medical director of HealthPartners Medical Group in Minneapolis and chair of the board of directors for the Institute for Clinical Systems Improvement (ICSI) in Bloomington, Minn. ICSI is a nonprofit group that spearheaded the development and launch of DIAMOND in 2008 in collaboration with more than 60 medical groups, hospitals, and health plans.
Specifically, each medical group participating in DIAMOND receives a monthly fee for every enrolled patient, said Dr. Mark D. Williams of the Mayo Clinic in Rochester, Minn. The fee, predetermined through collaboration with the state’s major insurers and represented by a single, specific billing code, covers the care "bundle," which includes depression screening and monitoring using the Patient Health Questionnaire (PHQ-9); weekly psychiatric consultation and case review; ongoing contact with the care manager; communication between the care manager, psychiatrist, and primary care physician; relapse prevention visits; and use of a patient registry.
"The fee addresses one of the main questions challenging health care improvement in this country: Who is going to pay for it?" Dr. Williams said in an interview. "The way health care is designed in the United States, practices are trying to manage lots of patients, because the only way they can survive is through volume. So, when you suggest trying a different model – one that requires hiring a resource care manager or pulling someone out of a different position from a busy clinic – the practices see risk. Their margins are so small already, committing to the change, even if it is evidence based, is difficult."
Because of the financial realities, the DIAMOND team had to figure out a way to implement the program in practices without the shadow of financial disincentives. "The challenge wasn’t proving it would work – there are lots of randomized controlled trials supporting the collaborative care model – the challenge was showing the practices that the costs wouldn’t be overwhelming," Dr. Williams said. "The promise of new income through the monthly fee was something that allowed the practices to go to their boards and argue that the new model would improve patient management without putting the practice at risk."
The DIAMOND protocol is built around the main elements of the Improving Mood: Promoting Access to Collaborative Treatment (IMPACT) program developed by Dr. Jürgen Unützer of the University of Washington (http://impact-uw.org/). These elements include:
• Standard and reliable use of the PHQ-9 for assessment and ongoing depression management;
• Use of an evidence-based guideline and a stepped-care approach for treatment modification or intensification;
• Development and use of a registry to monitor and track patients;
• Relapse-prevention training for patients reaching remission;
• Introduction of a trained care manager; and
• A formal relationship with a consulting psychiatrist.
The DIAMOND implementation differs from IMPACT, in that the DIAMOND care managers do not have to be nurses with psychiatric experience, according to Nancy Jaeckels, vice president of member relations and strategic initiatives for ICSI. Rather, DIAMOND has hired and trained various health care personnel to serve as care managers, including medical assistants, social workers, and licensed practical nurses, she said.
In participating practices, patients aged 18 years or older with a primary care diagnosis of major depression or dysthymia and a PHQ-9 score of at least 10 are enrolled in the DIAMOND program.
The care protocol includes an initial review of PHQ-9 results and symptoms with the primary care physician; an intake meeting with the care manager, during which patients are screened for other mental health or substance use problems; and weekly phone or in-person follow-up contact with the care manager to discuss treatment status and to complete the PHQ-9, the results of which the care manager enters into the patient registry, along with information on the patient’s medication, treatment adjustments, and behavior.
The DIAMOND protocol also includes a weekly meeting between the consulting psychiatrist and the care manager to review care and discuss patient-related issues or concerns; and periodic direct contact between the psychiatrist and the primary care provider, who is the medication prescriber, to assess treatment response and make adjustments as necessary.
"In some instances, there are patients who need more than DIAMOND can offer, so we spend a fair amount of energy linking with local mental health resources, advocating for the patients as much as possible," Dr. Williams said.
Patients enrolled in DIAMOND are covered for a maximum of 12 consecutive months, Ms. Jaeckels said. Before moving out of care management, they complete a relapse prevention plan with their care manager that includes an action plan if symptoms recur, she said.
The DIAMOND model addresses important deficiencies in the current management of depression in primary care, Dr. Williams said. "Even though we have outcome measures to tell when someone [with depression] is in trouble or improving, a lot of times primary care physicians don’t use these and instead ask questions like, ‘How is it going?’ or ‘How is the depression?’ That’s kind of like asking a patient with hypertension how he or she is doing without measuring blood pressure. It doesn’t make sense."
Another obstacle in traditional settings is that patients with depression "typically are not activated," Dr. Williams said. "They have trouble getting going and doing things, and they commonly feel overwhelmed by the fragmentation of the health care system, the difficulty getting appointments, problems with their prescriptions, to the point where they just stop doing what they should be doing and things get really bad," he explained. "This is where the care managers are so important, because they reach out to the patients, maintain the connection, and help them navigate."
The effort appears to be worth it, according to a review of primary outcome data from March 2008 through March 2010 reported on the public Minnesota Health Scores Web site. The site reported 6-month depression remission rates between 7% and 51%, compared with rates between 0% and 10% in clinics not using DIAMOND. An additional 16% of the DIAMOND patients experienced at least a 50% reduction in depression symptom severity – a rate nearly 10 times higher than that observed in the usual-care patients (www.mnhealthscores.org).
In addition to addressing symptoms of depression, the program leads to improvements in other areas, Dr. Williams said. "When patients are depressed, they tend not to deal with their other issues, such as asthma, diabetes, and alcohol abuse. As their symptoms improve and through the care collaboration, we start to identify some of those issues." This is one reason that, on paper, the health care costs during the first year of the program occasionally increase, he said.
"After some of these issues are addressed, the health care utilization costs actually drop substantially per patient, but that can take 3-4 years, and insurance companies are interested in the fiscal year."
Financial considerations, although addressed on the front end through the bundled fee, might ultimately present the biggest challenge to DIAMOND’s survival, Dr. Williams stated.
"Medicare and Medicaid have not yet agreed that this is worth paying for, despite having evidence that it works better than usual care and that the initial costs are likely to be offset quickly." This is because "there is a lot of pressure on them with universal health care to talk about the health care home," he said. "There’s a lot of uncertainty about whether the health care home is going to be a reality, so there is a hesitation to commit to other collaborative models."
In reality, the DIAMOND program, with its sustainable payment model, could be an important building block for the health care home, Dr. Williams stressed. In a recent case study evaluating the DIAMOND effort, he and his colleagues concluded that the model "offers a new direction" for achieving the goal of creating value in depression management, particularly at the mental health and primary care interface (Qual. Prim. Care 2010;18:327-33).
Dr. Williams and Dr. Rank have no relevant financial disclosures.
A depression care model aiming to bridge the gap between what is known about mental health obstacles and what is being done to minimize them has led to the successful communion of science and practice across Minnesota.
The model, called Depression Improvement Across Minnesota Offering a New Direction, or DIAMOND, uses a team-based approach to facilitate the screening, diagnosis, and management of depression among patients in 83 primary care practices across the state.
The DIAMOND approach, in which the care of patients who screen positive for depression in the primary care setting is choreographed by care managers and overseen by consulting psychiatrists, is not a novel one. In fact, a well-established body of evidence indicates that team care models improve outcomes in depression and reduce health care use costs over time (J. Occup. Environ. Med. 2008;50:459-67).
The unique aspect of the DIAMOND model is that it is the first depression treatment program in the country to integrate the team-based paradigm with a reimbursement structure that supports the provision of enhanced mental health care support in primary care clinics, according to Dr. Brian Rank. Dr. Rank is medical director of HealthPartners Medical Group in Minneapolis and chair of the board of directors for the Institute for Clinical Systems Improvement (ICSI) in Bloomington, Minn. ICSI is a nonprofit group that spearheaded the development and launch of DIAMOND in 2008 in collaboration with more than 60 medical groups, hospitals, and health plans.
Specifically, each medical group participating in DIAMOND receives a monthly fee for every enrolled patient, said Dr. Mark D. Williams of the Mayo Clinic in Rochester, Minn. The fee, predetermined through collaboration with the state’s major insurers and represented by a single, specific billing code, covers the care "bundle," which includes depression screening and monitoring using the Patient Health Questionnaire (PHQ-9); weekly psychiatric consultation and case review; ongoing contact with the care manager; communication between the care manager, psychiatrist, and primary care physician; relapse prevention visits; and use of a patient registry.
"The fee addresses one of the main questions challenging health care improvement in this country: Who is going to pay for it?" Dr. Williams said in an interview. "The way health care is designed in the United States, practices are trying to manage lots of patients, because the only way they can survive is through volume. So, when you suggest trying a different model – one that requires hiring a resource care manager or pulling someone out of a different position from a busy clinic – the practices see risk. Their margins are so small already, committing to the change, even if it is evidence based, is difficult."
Because of the financial realities, the DIAMOND team had to figure out a way to implement the program in practices without the shadow of financial disincentives. "The challenge wasn’t proving it would work – there are lots of randomized controlled trials supporting the collaborative care model – the challenge was showing the practices that the costs wouldn’t be overwhelming," Dr. Williams said. "The promise of new income through the monthly fee was something that allowed the practices to go to their boards and argue that the new model would improve patient management without putting the practice at risk."
The DIAMOND protocol is built around the main elements of the Improving Mood: Promoting Access to Collaborative Treatment (IMPACT) program developed by Dr. Jürgen Unützer of the University of Washington (http://impact-uw.org/). These elements include:
• Standard and reliable use of the PHQ-9 for assessment and ongoing depression management;
• Use of an evidence-based guideline and a stepped-care approach for treatment modification or intensification;
• Development and use of a registry to monitor and track patients;
• Relapse-prevention training for patients reaching remission;
• Introduction of a trained care manager; and
• A formal relationship with a consulting psychiatrist.
The DIAMOND implementation differs from IMPACT, in that the DIAMOND care managers do not have to be nurses with psychiatric experience, according to Nancy Jaeckels, vice president of member relations and strategic initiatives for ICSI. Rather, DIAMOND has hired and trained various health care personnel to serve as care managers, including medical assistants, social workers, and licensed practical nurses, she said.
In participating practices, patients aged 18 years or older with a primary care diagnosis of major depression or dysthymia and a PHQ-9 score of at least 10 are enrolled in the DIAMOND program.
The care protocol includes an initial review of PHQ-9 results and symptoms with the primary care physician; an intake meeting with the care manager, during which patients are screened for other mental health or substance use problems; and weekly phone or in-person follow-up contact with the care manager to discuss treatment status and to complete the PHQ-9, the results of which the care manager enters into the patient registry, along with information on the patient’s medication, treatment adjustments, and behavior.
The DIAMOND protocol also includes a weekly meeting between the consulting psychiatrist and the care manager to review care and discuss patient-related issues or concerns; and periodic direct contact between the psychiatrist and the primary care provider, who is the medication prescriber, to assess treatment response and make adjustments as necessary.
"In some instances, there are patients who need more than DIAMOND can offer, so we spend a fair amount of energy linking with local mental health resources, advocating for the patients as much as possible," Dr. Williams said.
Patients enrolled in DIAMOND are covered for a maximum of 12 consecutive months, Ms. Jaeckels said. Before moving out of care management, they complete a relapse prevention plan with their care manager that includes an action plan if symptoms recur, she said.
The DIAMOND model addresses important deficiencies in the current management of depression in primary care, Dr. Williams said. "Even though we have outcome measures to tell when someone [with depression] is in trouble or improving, a lot of times primary care physicians don’t use these and instead ask questions like, ‘How is it going?’ or ‘How is the depression?’ That’s kind of like asking a patient with hypertension how he or she is doing without measuring blood pressure. It doesn’t make sense."
Another obstacle in traditional settings is that patients with depression "typically are not activated," Dr. Williams said. "They have trouble getting going and doing things, and they commonly feel overwhelmed by the fragmentation of the health care system, the difficulty getting appointments, problems with their prescriptions, to the point where they just stop doing what they should be doing and things get really bad," he explained. "This is where the care managers are so important, because they reach out to the patients, maintain the connection, and help them navigate."
The effort appears to be worth it, according to a review of primary outcome data from March 2008 through March 2010 reported on the public Minnesota Health Scores Web site. The site reported 6-month depression remission rates between 7% and 51%, compared with rates between 0% and 10% in clinics not using DIAMOND. An additional 16% of the DIAMOND patients experienced at least a 50% reduction in depression symptom severity – a rate nearly 10 times higher than that observed in the usual-care patients (www.mnhealthscores.org).
In addition to addressing symptoms of depression, the program leads to improvements in other areas, Dr. Williams said. "When patients are depressed, they tend not to deal with their other issues, such as asthma, diabetes, and alcohol abuse. As their symptoms improve and through the care collaboration, we start to identify some of those issues." This is one reason that, on paper, the health care costs during the first year of the program occasionally increase, he said.
"After some of these issues are addressed, the health care utilization costs actually drop substantially per patient, but that can take 3-4 years, and insurance companies are interested in the fiscal year."
Financial considerations, although addressed on the front end through the bundled fee, might ultimately present the biggest challenge to DIAMOND’s survival, Dr. Williams stated.
"Medicare and Medicaid have not yet agreed that this is worth paying for, despite having evidence that it works better than usual care and that the initial costs are likely to be offset quickly." This is because "there is a lot of pressure on them with universal health care to talk about the health care home," he said. "There’s a lot of uncertainty about whether the health care home is going to be a reality, so there is a hesitation to commit to other collaborative models."
In reality, the DIAMOND program, with its sustainable payment model, could be an important building block for the health care home, Dr. Williams stressed. In a recent case study evaluating the DIAMOND effort, he and his colleagues concluded that the model "offers a new direction" for achieving the goal of creating value in depression management, particularly at the mental health and primary care interface (Qual. Prim. Care 2010;18:327-33).
Dr. Williams and Dr. Rank have no relevant financial disclosures.
New Fungal Infection Guidelines Include Novel Agents
The choice of treatment for the management of adult pulmonary fungal infections should be based on diagnostic findings and individual risk factors, according to a new policy statement issued by the American Thoracic Society. "In most cases, treatment of fungal infections must be based on the causative fungus, the severity of disease, and the clinical features of each patient," the authors wrote.
The policy statement provides organism- and infection-site specific guidelines for therapy, including dosing recommendations, and incorporates the range of novel antifungal medications, such as the extended-spectrum triazoles and echinocandins, that have been introduced since the previous guidelines were published in 1988, according to Dr. Andrew Limper of the Mayo Clinic in Rochester, Minn., and his colleagues on the American Thoracic Society (ATS) Fungal Infections Working Group.
In particular, the recommendations outline the management of endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections with increased prevalence in immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections, such as zygomycoses, hyalohyphomycoses, the phaeohyphomycoses, and infections related to Trichosporon species (Am. J. Respir. Crit. Care. Med. 2011;183:96-128).
Endemic Mycoses. The guidelines recommend treatment with itraconazole for mild to moderate histoplasmosis, sporotrichosis, and blastomycosis, and treatment with amphotericin B for severe disease (followed by itraconazole in patients with sporotrichosis). Patients with severe histoplasmosis with diffuse pulmonary infiltrates and critically ill patients with severe pulmonary blastomycosis may require systemic steroid therapy, as well. Further, for patients with pulmonary blastomycosis and concomitant CNS involvement, combination therapy with liposomal amphotericin B (vs. amphotericin B deoxycholate) and fluconazole "should be considered due to theoretic better CNS penetration," the authors wrote.
Antifungal therapy is not recommended for primary pulmonary coccidioidomycosis in immunocompetent patients who have no risk factors for dissemination, while patients with disseminated infection should be treated with an extended-spectrum triazole, according to the guidelines, which also specify that critically ill patients with disseminated paracoccidioidomycosis should be treated initially with amphotericin B, followed by ketoconazole, itraconazole, or sulfadiazine.
Immunocompromised Patients. The treatment options for fungal infections in patients with compromised immune systems, including transplant patients, those being treated for autoimmune inflammatory conditions, and HIV-infected patients, include oral trimethoprim and sulfamethoxazole, oral primaquine plus clindamycin, or oral atovaquone for mild to moderate Pneumocystis pneumonia. Patients with moderate to severe disease should be given trimethoprim, sulfamethoxazole, and possibly prednisone, the guidelines recommend.
Emerging Fungal Infections. "The management of emerging or rare fungi is supported by limited evidence-based studies with no randomized, blinded comparative studies," the authors wrote, noting that treatment recommendations are thus based on clinical experience and in vitro susceptibility testing. Because the majority of affected patients are immunocompromised, "a primary strategy for management of these infections with underlying diseases is to maximally reduce immunosuppressive drugs, provide immunostimulants, and/or rapidly control the underlying diseases or conditions, such as HIV infection, diabetes, and/or chemotherapy-induced neutropenia," they stated.
Secondarily, particularly in the angioinvasive zygomycoses, necrotic tissues, cysts, or true abscesses should be debulked or debrided, they emphasized.
The third management strategy includes specific antifungal recommendations, such as amphotericin B for zygomycosis; voriconazole, posaconazole, or lipid formulations of amphotericin B for fusariosis; voriconazole or posaconazole for scedosporiosis; itraconazole, voriconazole, or posaconazole for phaeohyphomycoses; and, possibly, voriconazole, posaconazole, or itraconazole for trichosporonis and Paecilomyces infections.
"The exact dosing and duration of treatment for these emerging, rare infections are not precise, and consultation with an expert in infectious disease regarding these clinical decisions should be considered," the authors stressed.
The policy statement also includes recommendations for the treatment of Candida and Aspergillus infections, which are becoming increasingly common in the intensive care unit, the authors stated. For candidemia, the guidelines recommend that all existing central venous catheters should be removed, if possible, or a new placement site should be obtained and initial antifungal treatment should be with fluconazole, an amphotericin B formulation, an echinocandin, or a combination of fluconazole and amphotericin. With respect to Aspergillus infections, the guidelines recommend intravenous voriconazole or liposomal amphotericin B for invasive pulmonary aspergillosis; voriconazole or itraconazole for mild to moderate chronic necrotizing aspergillosis; and liposomal amphotericin B or intravenous voriconazole for severe chronic necrotizing aspergillosis.
The authors reported financial relationships with AlphaMed Pharmaceuticals, Pfizer, Ortho-McNeil, MiraBella Technologies, AstraZeneca, GlaxoSmithKline, Bayer, Novartis, Aradigm, Astellas, Enzon, Merck, and Schering-Plough.
The choice of treatment for the management of adult pulmonary fungal infections should be based on diagnostic findings and individual risk factors, according to a new policy statement issued by the American Thoracic Society. "In most cases, treatment of fungal infections must be based on the causative fungus, the severity of disease, and the clinical features of each patient," the authors wrote.
The policy statement provides organism- and infection-site specific guidelines for therapy, including dosing recommendations, and incorporates the range of novel antifungal medications, such as the extended-spectrum triazoles and echinocandins, that have been introduced since the previous guidelines were published in 1988, according to Dr. Andrew Limper of the Mayo Clinic in Rochester, Minn., and his colleagues on the American Thoracic Society (ATS) Fungal Infections Working Group.
In particular, the recommendations outline the management of endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections with increased prevalence in immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections, such as zygomycoses, hyalohyphomycoses, the phaeohyphomycoses, and infections related to Trichosporon species (Am. J. Respir. Crit. Care. Med. 2011;183:96-128).
Endemic Mycoses. The guidelines recommend treatment with itraconazole for mild to moderate histoplasmosis, sporotrichosis, and blastomycosis, and treatment with amphotericin B for severe disease (followed by itraconazole in patients with sporotrichosis). Patients with severe histoplasmosis with diffuse pulmonary infiltrates and critically ill patients with severe pulmonary blastomycosis may require systemic steroid therapy, as well. Further, for patients with pulmonary blastomycosis and concomitant CNS involvement, combination therapy with liposomal amphotericin B (vs. amphotericin B deoxycholate) and fluconazole "should be considered due to theoretic better CNS penetration," the authors wrote.
Antifungal therapy is not recommended for primary pulmonary coccidioidomycosis in immunocompetent patients who have no risk factors for dissemination, while patients with disseminated infection should be treated with an extended-spectrum triazole, according to the guidelines, which also specify that critically ill patients with disseminated paracoccidioidomycosis should be treated initially with amphotericin B, followed by ketoconazole, itraconazole, or sulfadiazine.
Immunocompromised Patients. The treatment options for fungal infections in patients with compromised immune systems, including transplant patients, those being treated for autoimmune inflammatory conditions, and HIV-infected patients, include oral trimethoprim and sulfamethoxazole, oral primaquine plus clindamycin, or oral atovaquone for mild to moderate Pneumocystis pneumonia. Patients with moderate to severe disease should be given trimethoprim, sulfamethoxazole, and possibly prednisone, the guidelines recommend.
Emerging Fungal Infections. "The management of emerging or rare fungi is supported by limited evidence-based studies with no randomized, blinded comparative studies," the authors wrote, noting that treatment recommendations are thus based on clinical experience and in vitro susceptibility testing. Because the majority of affected patients are immunocompromised, "a primary strategy for management of these infections with underlying diseases is to maximally reduce immunosuppressive drugs, provide immunostimulants, and/or rapidly control the underlying diseases or conditions, such as HIV infection, diabetes, and/or chemotherapy-induced neutropenia," they stated.
Secondarily, particularly in the angioinvasive zygomycoses, necrotic tissues, cysts, or true abscesses should be debulked or debrided, they emphasized.
The third management strategy includes specific antifungal recommendations, such as amphotericin B for zygomycosis; voriconazole, posaconazole, or lipid formulations of amphotericin B for fusariosis; voriconazole or posaconazole for scedosporiosis; itraconazole, voriconazole, or posaconazole for phaeohyphomycoses; and, possibly, voriconazole, posaconazole, or itraconazole for trichosporonis and Paecilomyces infections.
"The exact dosing and duration of treatment for these emerging, rare infections are not precise, and consultation with an expert in infectious disease regarding these clinical decisions should be considered," the authors stressed.
The policy statement also includes recommendations for the treatment of Candida and Aspergillus infections, which are becoming increasingly common in the intensive care unit, the authors stated. For candidemia, the guidelines recommend that all existing central venous catheters should be removed, if possible, or a new placement site should be obtained and initial antifungal treatment should be with fluconazole, an amphotericin B formulation, an echinocandin, or a combination of fluconazole and amphotericin. With respect to Aspergillus infections, the guidelines recommend intravenous voriconazole or liposomal amphotericin B for invasive pulmonary aspergillosis; voriconazole or itraconazole for mild to moderate chronic necrotizing aspergillosis; and liposomal amphotericin B or intravenous voriconazole for severe chronic necrotizing aspergillosis.
The authors reported financial relationships with AlphaMed Pharmaceuticals, Pfizer, Ortho-McNeil, MiraBella Technologies, AstraZeneca, GlaxoSmithKline, Bayer, Novartis, Aradigm, Astellas, Enzon, Merck, and Schering-Plough.
The choice of treatment for the management of adult pulmonary fungal infections should be based on diagnostic findings and individual risk factors, according to a new policy statement issued by the American Thoracic Society. "In most cases, treatment of fungal infections must be based on the causative fungus, the severity of disease, and the clinical features of each patient," the authors wrote.
The policy statement provides organism- and infection-site specific guidelines for therapy, including dosing recommendations, and incorporates the range of novel antifungal medications, such as the extended-spectrum triazoles and echinocandins, that have been introduced since the previous guidelines were published in 1988, according to Dr. Andrew Limper of the Mayo Clinic in Rochester, Minn., and his colleagues on the American Thoracic Society (ATS) Fungal Infections Working Group.
In particular, the recommendations outline the management of endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections with increased prevalence in immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections, such as zygomycoses, hyalohyphomycoses, the phaeohyphomycoses, and infections related to Trichosporon species (Am. J. Respir. Crit. Care. Med. 2011;183:96-128).
Endemic Mycoses. The guidelines recommend treatment with itraconazole for mild to moderate histoplasmosis, sporotrichosis, and blastomycosis, and treatment with amphotericin B for severe disease (followed by itraconazole in patients with sporotrichosis). Patients with severe histoplasmosis with diffuse pulmonary infiltrates and critically ill patients with severe pulmonary blastomycosis may require systemic steroid therapy, as well. Further, for patients with pulmonary blastomycosis and concomitant CNS involvement, combination therapy with liposomal amphotericin B (vs. amphotericin B deoxycholate) and fluconazole "should be considered due to theoretic better CNS penetration," the authors wrote.
Antifungal therapy is not recommended for primary pulmonary coccidioidomycosis in immunocompetent patients who have no risk factors for dissemination, while patients with disseminated infection should be treated with an extended-spectrum triazole, according to the guidelines, which also specify that critically ill patients with disseminated paracoccidioidomycosis should be treated initially with amphotericin B, followed by ketoconazole, itraconazole, or sulfadiazine.
Immunocompromised Patients. The treatment options for fungal infections in patients with compromised immune systems, including transplant patients, those being treated for autoimmune inflammatory conditions, and HIV-infected patients, include oral trimethoprim and sulfamethoxazole, oral primaquine plus clindamycin, or oral atovaquone for mild to moderate Pneumocystis pneumonia. Patients with moderate to severe disease should be given trimethoprim, sulfamethoxazole, and possibly prednisone, the guidelines recommend.
Emerging Fungal Infections. "The management of emerging or rare fungi is supported by limited evidence-based studies with no randomized, blinded comparative studies," the authors wrote, noting that treatment recommendations are thus based on clinical experience and in vitro susceptibility testing. Because the majority of affected patients are immunocompromised, "a primary strategy for management of these infections with underlying diseases is to maximally reduce immunosuppressive drugs, provide immunostimulants, and/or rapidly control the underlying diseases or conditions, such as HIV infection, diabetes, and/or chemotherapy-induced neutropenia," they stated.
Secondarily, particularly in the angioinvasive zygomycoses, necrotic tissues, cysts, or true abscesses should be debulked or debrided, they emphasized.
The third management strategy includes specific antifungal recommendations, such as amphotericin B for zygomycosis; voriconazole, posaconazole, or lipid formulations of amphotericin B for fusariosis; voriconazole or posaconazole for scedosporiosis; itraconazole, voriconazole, or posaconazole for phaeohyphomycoses; and, possibly, voriconazole, posaconazole, or itraconazole for trichosporonis and Paecilomyces infections.
"The exact dosing and duration of treatment for these emerging, rare infections are not precise, and consultation with an expert in infectious disease regarding these clinical decisions should be considered," the authors stressed.
The policy statement also includes recommendations for the treatment of Candida and Aspergillus infections, which are becoming increasingly common in the intensive care unit, the authors stated. For candidemia, the guidelines recommend that all existing central venous catheters should be removed, if possible, or a new placement site should be obtained and initial antifungal treatment should be with fluconazole, an amphotericin B formulation, an echinocandin, or a combination of fluconazole and amphotericin. With respect to Aspergillus infections, the guidelines recommend intravenous voriconazole or liposomal amphotericin B for invasive pulmonary aspergillosis; voriconazole or itraconazole for mild to moderate chronic necrotizing aspergillosis; and liposomal amphotericin B or intravenous voriconazole for severe chronic necrotizing aspergillosis.
The authors reported financial relationships with AlphaMed Pharmaceuticals, Pfizer, Ortho-McNeil, MiraBella Technologies, AstraZeneca, GlaxoSmithKline, Bayer, Novartis, Aradigm, Astellas, Enzon, Merck, and Schering-Plough.
FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
New Fungal Infection Guidelines Include Novel Agents
The choice of treatment for the management of adult pulmonary fungal infections should be based on diagnostic findings and individual risk factors, according to a new policy statement issued by the American Thoracic Society. "In most cases, treatment of fungal infections must be based on the causative fungus, the severity of disease, and the clinical features of each patient," the authors wrote.
The policy statement provides organism- and infection-site specific guidelines for therapy, including dosing recommendations, and incorporates the range of novel antifungal medications, such as the extended-spectrum triazoles and echinocandins, that have been introduced since the previous guidelines were published in 1988, according to Dr. Andrew Limper of the Mayo Clinic in Rochester, Minn., and his colleagues on the American Thoracic Society (ATS) Fungal Infections Working Group.
In particular, the recommendations outline the management of endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections with increased prevalence in immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections, such as zygomycoses, hyalohyphomycoses, the phaeohyphomycoses, and infections related to Trichosporon species (Am. J. Respir. Crit. Care. Med. 2011;183:96-128).
Endemic Mycoses. The guidelines recommend treatment with itraconazole for mild to moderate histoplasmosis, sporotrichosis, and blastomycosis, and treatment with amphotericin B for severe disease (followed by itraconazole in patients with sporotrichosis). Patients with severe histoplasmosis with diffuse pulmonary infiltrates and critically ill patients with severe pulmonary blastomycosis may require systemic steroid therapy, as well. Further, for patients with pulmonary blastomycosis and concomitant CNS involvement, combination therapy with liposomal amphotericin B (vs. amphotericin B deoxycholate) and fluconazole "should be considered due to theoretic better CNS penetration," the authors wrote.
Antifungal therapy is not recommended for primary pulmonary coccidioidomycosis in immunocompetent patients who have no risk factors for dissemination, while patients with disseminated infection should be treated with an extended-spectrum triazole, according to the guidelines, which also specify that critically ill patients with disseminated paracoccidioidomycosis should be treated initially with amphotericin B, followed by ketoconazole, itraconazole, or sulfadiazine.
Immunocompromised Patients. The treatment options for fungal infections in patients with compromised immune systems, including transplant patients, those being treated for autoimmune inflammatory conditions, and HIV-infected patients, include oral trimethoprim and sulfamethoxazole, oral primaquine plus clindamycin, or oral atovaquone for mild to moderate Pneumocystis pneumonia. Patients with moderate to severe disease should be given trimethoprim, sulfamethoxazole, and possibly prednisone, the guidelines recommend.
Emerging Fungal Infections. "The management of emerging or rare fungi is supported by limited evidence-based studies with no randomized, blinded comparative studies," the authors wrote, noting that treatment recommendations are thus based on clinical experience and in vitro susceptibility testing. Because the majority of affected patients are immunocompromised, "a primary strategy for management of these infections with underlying diseases is to maximally reduce immunosuppressive drugs, provide immunostimulants, and/or rapidly control the underlying diseases or conditions, such as HIV infection, diabetes, and/or chemotherapy-induced neutropenia," they stated.
Secondarily, particularly in the angioinvasive zygomycoses, necrotic tissues, cysts, or true abscesses should be debulked or debrided, they emphasized.
The third management strategy includes specific antifungal recommendations, such as amphotericin B for zygomycosis; voriconazole, posaconazole, or lipid formulations of amphotericin B for fusariosis; voriconazole or posaconazole for scedosporiosis; itraconazole, voriconazole, or posaconazole for phaeohyphomycoses; and, possibly, voriconazole, posaconazole, or itraconazole for trichosporonis and Paecilomyces infections.
"The exact dosing and duration of treatment for these emerging, rare infections are not precise, and consultation with an expert in infectious disease regarding these clinical decisions should be considered," the authors stressed.
The policy statement also includes recommendations for the treatment of Candida and Aspergillus infections, which are becoming increasingly common in the intensive care unit, the authors stated. For candidemia, the guidelines recommend that all existing central venous catheters should be removed, if possible, or a new placement site should be obtained and initial antifungal treatment should be with fluconazole, an amphotericin B formulation, an echinocandin, or a combination of fluconazole and amphotericin. With respect to Aspergillus infections, the guidelines recommend intravenous voriconazole or liposomal amphotericin B for invasive pulmonary aspergillosis; voriconazole or itraconazole for mild to moderate chronic necrotizing aspergillosis; and liposomal amphotericin B or intravenous voriconazole for severe chronic necrotizing aspergillosis.
The authors reported financial relationships with AlphaMed Pharmaceuticals, Pfizer, Ortho-McNeil, MiraBella Technologies, AstraZeneca, GlaxoSmithKline, Bayer, Novartis, Aradigm, Astellas, Enzon, Merck, and Schering-Plough.
The choice of treatment for the management of adult pulmonary fungal infections should be based on diagnostic findings and individual risk factors, according to a new policy statement issued by the American Thoracic Society. "In most cases, treatment of fungal infections must be based on the causative fungus, the severity of disease, and the clinical features of each patient," the authors wrote.
The policy statement provides organism- and infection-site specific guidelines for therapy, including dosing recommendations, and incorporates the range of novel antifungal medications, such as the extended-spectrum triazoles and echinocandins, that have been introduced since the previous guidelines were published in 1988, according to Dr. Andrew Limper of the Mayo Clinic in Rochester, Minn., and his colleagues on the American Thoracic Society (ATS) Fungal Infections Working Group.
In particular, the recommendations outline the management of endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections with increased prevalence in immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections, such as zygomycoses, hyalohyphomycoses, the phaeohyphomycoses, and infections related to Trichosporon species (Am. J. Respir. Crit. Care. Med. 2011;183:96-128).
Endemic Mycoses. The guidelines recommend treatment with itraconazole for mild to moderate histoplasmosis, sporotrichosis, and blastomycosis, and treatment with amphotericin B for severe disease (followed by itraconazole in patients with sporotrichosis). Patients with severe histoplasmosis with diffuse pulmonary infiltrates and critically ill patients with severe pulmonary blastomycosis may require systemic steroid therapy, as well. Further, for patients with pulmonary blastomycosis and concomitant CNS involvement, combination therapy with liposomal amphotericin B (vs. amphotericin B deoxycholate) and fluconazole "should be considered due to theoretic better CNS penetration," the authors wrote.
Antifungal therapy is not recommended for primary pulmonary coccidioidomycosis in immunocompetent patients who have no risk factors for dissemination, while patients with disseminated infection should be treated with an extended-spectrum triazole, according to the guidelines, which also specify that critically ill patients with disseminated paracoccidioidomycosis should be treated initially with amphotericin B, followed by ketoconazole, itraconazole, or sulfadiazine.
Immunocompromised Patients. The treatment options for fungal infections in patients with compromised immune systems, including transplant patients, those being treated for autoimmune inflammatory conditions, and HIV-infected patients, include oral trimethoprim and sulfamethoxazole, oral primaquine plus clindamycin, or oral atovaquone for mild to moderate Pneumocystis pneumonia. Patients with moderate to severe disease should be given trimethoprim, sulfamethoxazole, and possibly prednisone, the guidelines recommend.
Emerging Fungal Infections. "The management of emerging or rare fungi is supported by limited evidence-based studies with no randomized, blinded comparative studies," the authors wrote, noting that treatment recommendations are thus based on clinical experience and in vitro susceptibility testing. Because the majority of affected patients are immunocompromised, "a primary strategy for management of these infections with underlying diseases is to maximally reduce immunosuppressive drugs, provide immunostimulants, and/or rapidly control the underlying diseases or conditions, such as HIV infection, diabetes, and/or chemotherapy-induced neutropenia," they stated.
Secondarily, particularly in the angioinvasive zygomycoses, necrotic tissues, cysts, or true abscesses should be debulked or debrided, they emphasized.
The third management strategy includes specific antifungal recommendations, such as amphotericin B for zygomycosis; voriconazole, posaconazole, or lipid formulations of amphotericin B for fusariosis; voriconazole or posaconazole for scedosporiosis; itraconazole, voriconazole, or posaconazole for phaeohyphomycoses; and, possibly, voriconazole, posaconazole, or itraconazole for trichosporonis and Paecilomyces infections.
"The exact dosing and duration of treatment for these emerging, rare infections are not precise, and consultation with an expert in infectious disease regarding these clinical decisions should be considered," the authors stressed.
The policy statement also includes recommendations for the treatment of Candida and Aspergillus infections, which are becoming increasingly common in the intensive care unit, the authors stated. For candidemia, the guidelines recommend that all existing central venous catheters should be removed, if possible, or a new placement site should be obtained and initial antifungal treatment should be with fluconazole, an amphotericin B formulation, an echinocandin, or a combination of fluconazole and amphotericin. With respect to Aspergillus infections, the guidelines recommend intravenous voriconazole or liposomal amphotericin B for invasive pulmonary aspergillosis; voriconazole or itraconazole for mild to moderate chronic necrotizing aspergillosis; and liposomal amphotericin B or intravenous voriconazole for severe chronic necrotizing aspergillosis.
The authors reported financial relationships with AlphaMed Pharmaceuticals, Pfizer, Ortho-McNeil, MiraBella Technologies, AstraZeneca, GlaxoSmithKline, Bayer, Novartis, Aradigm, Astellas, Enzon, Merck, and Schering-Plough.
The choice of treatment for the management of adult pulmonary fungal infections should be based on diagnostic findings and individual risk factors, according to a new policy statement issued by the American Thoracic Society. "In most cases, treatment of fungal infections must be based on the causative fungus, the severity of disease, and the clinical features of each patient," the authors wrote.
The policy statement provides organism- and infection-site specific guidelines for therapy, including dosing recommendations, and incorporates the range of novel antifungal medications, such as the extended-spectrum triazoles and echinocandins, that have been introduced since the previous guidelines were published in 1988, according to Dr. Andrew Limper of the Mayo Clinic in Rochester, Minn., and his colleagues on the American Thoracic Society (ATS) Fungal Infections Working Group.
In particular, the recommendations outline the management of endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections with increased prevalence in immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections, such as zygomycoses, hyalohyphomycoses, the phaeohyphomycoses, and infections related to Trichosporon species (Am. J. Respir. Crit. Care. Med. 2011;183:96-128).
Endemic Mycoses. The guidelines recommend treatment with itraconazole for mild to moderate histoplasmosis, sporotrichosis, and blastomycosis, and treatment with amphotericin B for severe disease (followed by itraconazole in patients with sporotrichosis). Patients with severe histoplasmosis with diffuse pulmonary infiltrates and critically ill patients with severe pulmonary blastomycosis may require systemic steroid therapy, as well. Further, for patients with pulmonary blastomycosis and concomitant CNS involvement, combination therapy with liposomal amphotericin B (vs. amphotericin B deoxycholate) and fluconazole "should be considered due to theoretic better CNS penetration," the authors wrote.
Antifungal therapy is not recommended for primary pulmonary coccidioidomycosis in immunocompetent patients who have no risk factors for dissemination, while patients with disseminated infection should be treated with an extended-spectrum triazole, according to the guidelines, which also specify that critically ill patients with disseminated paracoccidioidomycosis should be treated initially with amphotericin B, followed by ketoconazole, itraconazole, or sulfadiazine.
Immunocompromised Patients. The treatment options for fungal infections in patients with compromised immune systems, including transplant patients, those being treated for autoimmune inflammatory conditions, and HIV-infected patients, include oral trimethoprim and sulfamethoxazole, oral primaquine plus clindamycin, or oral atovaquone for mild to moderate Pneumocystis pneumonia. Patients with moderate to severe disease should be given trimethoprim, sulfamethoxazole, and possibly prednisone, the guidelines recommend.
Emerging Fungal Infections. "The management of emerging or rare fungi is supported by limited evidence-based studies with no randomized, blinded comparative studies," the authors wrote, noting that treatment recommendations are thus based on clinical experience and in vitro susceptibility testing. Because the majority of affected patients are immunocompromised, "a primary strategy for management of these infections with underlying diseases is to maximally reduce immunosuppressive drugs, provide immunostimulants, and/or rapidly control the underlying diseases or conditions, such as HIV infection, diabetes, and/or chemotherapy-induced neutropenia," they stated.
Secondarily, particularly in the angioinvasive zygomycoses, necrotic tissues, cysts, or true abscesses should be debulked or debrided, they emphasized.
The third management strategy includes specific antifungal recommendations, such as amphotericin B for zygomycosis; voriconazole, posaconazole, or lipid formulations of amphotericin B for fusariosis; voriconazole or posaconazole for scedosporiosis; itraconazole, voriconazole, or posaconazole for phaeohyphomycoses; and, possibly, voriconazole, posaconazole, or itraconazole for trichosporonis and Paecilomyces infections.
"The exact dosing and duration of treatment for these emerging, rare infections are not precise, and consultation with an expert in infectious disease regarding these clinical decisions should be considered," the authors stressed.
The policy statement also includes recommendations for the treatment of Candida and Aspergillus infections, which are becoming increasingly common in the intensive care unit, the authors stated. For candidemia, the guidelines recommend that all existing central venous catheters should be removed, if possible, or a new placement site should be obtained and initial antifungal treatment should be with fluconazole, an amphotericin B formulation, an echinocandin, or a combination of fluconazole and amphotericin. With respect to Aspergillus infections, the guidelines recommend intravenous voriconazole or liposomal amphotericin B for invasive pulmonary aspergillosis; voriconazole or itraconazole for mild to moderate chronic necrotizing aspergillosis; and liposomal amphotericin B or intravenous voriconazole for severe chronic necrotizing aspergillosis.
The authors reported financial relationships with AlphaMed Pharmaceuticals, Pfizer, Ortho-McNeil, MiraBella Technologies, AstraZeneca, GlaxoSmithKline, Bayer, Novartis, Aradigm, Astellas, Enzon, Merck, and Schering-Plough.
FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Adult ADHD Symptoms Increase Risk of Dementia With Lewy Bodies
Adults with symptoms of attention-deficit/hyperactivity disorder may be at increased risk for developing dementia with Lewy bodies as they age, according to a case-control study published in the European Journal of Neurology.
Patients who developed dementia with Lewy bodies (DLB) in older age had a history of ADHD symptoms in adulthood at more than three times the rate of healthy older adults or patients with Alzheimer’s disease, reported Dr. Angel Golimstok and colleagues at the Hospital Italiano Buenos Aires (Argentina).
The study is the first to establish a clear link between adult ADHD symptoms and DLB.
To investigate the possibility that ADHD symptoms may precede DLB, the researchers recruited a representative sample of patients with dementia and healthy controls from the membership of a large prepaid health maintenance organization model during 2000-2005. Two neurologists blinded to the purpose of the study used the DSM-IV and the Wender Utah Rating Scale to assess retrospective reports from family members or close friends about the patients’ previous symptoms of ADHD (Eur. J. Neurol. 2011;18:78-84).
Dr. Golimstok and associates determined that 52 (48%) of 109 patients with DLB had previously suffered from symptoms of adult ADHD, compared with 38 (15%) of 251 patients with Alzheimer’s disease (odds ratio 5.1) and 23 (15%) of 149 healthy control patients (OR 4.9). This meant that DLB patients were about five times more likely to have had ADHD symptoms than were Alzheimer’s disease patients or healthy controls.
Scores on parts of the rating scale that measured impulsivity and hyperactivity were significantly higher in patients with DLB, compared with both the Alzheimer’s disease and healthy control groups, they noted.
The investigators suggested that the association between ADHD symptoms and DLB may be explained by a common neurotransmitter pathway dysfunction. "In ADHD there are low levels of tonic [dopamine], and the abnormalities in [noradrenaline] may affect the maturation of central dopaminergic systems," they wrote. "This may be a risk factor for the development of DLB as well as Parkinson’s disease."
Although it is possible that both diseases may lie on a continuum of a single disease beginning with ADHD manifested in childhood and continuing into adulthood as DLB "when neuronal loss and gliosis in the substantia nigra, locus coeruleus, and nucleus basalis of Meynert occur," the authors doubted that this hypothesis could be true, because low dopamine levels in ADHD are not initially associated with Parkinsonlike or DLB symptoms.
The study findings may be limited by several factors, including the possibility that ADHD may occur more frequently in individuals with a personality type that could be linked to DLB or that "ADHD exposure could be a reflection of DLB not yet recognized," the authors stated.
The authors disclosed having no relevant financial conflicts.
Adults with symptoms of attention-deficit/hyperactivity disorder may be at increased risk for developing dementia with Lewy bodies as they age, according to a case-control study published in the European Journal of Neurology.
Patients who developed dementia with Lewy bodies (DLB) in older age had a history of ADHD symptoms in adulthood at more than three times the rate of healthy older adults or patients with Alzheimer’s disease, reported Dr. Angel Golimstok and colleagues at the Hospital Italiano Buenos Aires (Argentina).
The study is the first to establish a clear link between adult ADHD symptoms and DLB.
To investigate the possibility that ADHD symptoms may precede DLB, the researchers recruited a representative sample of patients with dementia and healthy controls from the membership of a large prepaid health maintenance organization model during 2000-2005. Two neurologists blinded to the purpose of the study used the DSM-IV and the Wender Utah Rating Scale to assess retrospective reports from family members or close friends about the patients’ previous symptoms of ADHD (Eur. J. Neurol. 2011;18:78-84).
Dr. Golimstok and associates determined that 52 (48%) of 109 patients with DLB had previously suffered from symptoms of adult ADHD, compared with 38 (15%) of 251 patients with Alzheimer’s disease (odds ratio 5.1) and 23 (15%) of 149 healthy control patients (OR 4.9). This meant that DLB patients were about five times more likely to have had ADHD symptoms than were Alzheimer’s disease patients or healthy controls.
Scores on parts of the rating scale that measured impulsivity and hyperactivity were significantly higher in patients with DLB, compared with both the Alzheimer’s disease and healthy control groups, they noted.
The investigators suggested that the association between ADHD symptoms and DLB may be explained by a common neurotransmitter pathway dysfunction. "In ADHD there are low levels of tonic [dopamine], and the abnormalities in [noradrenaline] may affect the maturation of central dopaminergic systems," they wrote. "This may be a risk factor for the development of DLB as well as Parkinson’s disease."
Although it is possible that both diseases may lie on a continuum of a single disease beginning with ADHD manifested in childhood and continuing into adulthood as DLB "when neuronal loss and gliosis in the substantia nigra, locus coeruleus, and nucleus basalis of Meynert occur," the authors doubted that this hypothesis could be true, because low dopamine levels in ADHD are not initially associated with Parkinsonlike or DLB symptoms.
The study findings may be limited by several factors, including the possibility that ADHD may occur more frequently in individuals with a personality type that could be linked to DLB or that "ADHD exposure could be a reflection of DLB not yet recognized," the authors stated.
The authors disclosed having no relevant financial conflicts.
Adults with symptoms of attention-deficit/hyperactivity disorder may be at increased risk for developing dementia with Lewy bodies as they age, according to a case-control study published in the European Journal of Neurology.
Patients who developed dementia with Lewy bodies (DLB) in older age had a history of ADHD symptoms in adulthood at more than three times the rate of healthy older adults or patients with Alzheimer’s disease, reported Dr. Angel Golimstok and colleagues at the Hospital Italiano Buenos Aires (Argentina).
The study is the first to establish a clear link between adult ADHD symptoms and DLB.
To investigate the possibility that ADHD symptoms may precede DLB, the researchers recruited a representative sample of patients with dementia and healthy controls from the membership of a large prepaid health maintenance organization model during 2000-2005. Two neurologists blinded to the purpose of the study used the DSM-IV and the Wender Utah Rating Scale to assess retrospective reports from family members or close friends about the patients’ previous symptoms of ADHD (Eur. J. Neurol. 2011;18:78-84).
Dr. Golimstok and associates determined that 52 (48%) of 109 patients with DLB had previously suffered from symptoms of adult ADHD, compared with 38 (15%) of 251 patients with Alzheimer’s disease (odds ratio 5.1) and 23 (15%) of 149 healthy control patients (OR 4.9). This meant that DLB patients were about five times more likely to have had ADHD symptoms than were Alzheimer’s disease patients or healthy controls.
Scores on parts of the rating scale that measured impulsivity and hyperactivity were significantly higher in patients with DLB, compared with both the Alzheimer’s disease and healthy control groups, they noted.
The investigators suggested that the association between ADHD symptoms and DLB may be explained by a common neurotransmitter pathway dysfunction. "In ADHD there are low levels of tonic [dopamine], and the abnormalities in [noradrenaline] may affect the maturation of central dopaminergic systems," they wrote. "This may be a risk factor for the development of DLB as well as Parkinson’s disease."
Although it is possible that both diseases may lie on a continuum of a single disease beginning with ADHD manifested in childhood and continuing into adulthood as DLB "when neuronal loss and gliosis in the substantia nigra, locus coeruleus, and nucleus basalis of Meynert occur," the authors doubted that this hypothesis could be true, because low dopamine levels in ADHD are not initially associated with Parkinsonlike or DLB symptoms.
The study findings may be limited by several factors, including the possibility that ADHD may occur more frequently in individuals with a personality type that could be linked to DLB or that "ADHD exposure could be a reflection of DLB not yet recognized," the authors stated.
The authors disclosed having no relevant financial conflicts.
FROM THE EUROPEAN JOURNAL OF NEUROLOGY
Major Finding: ADHD symptoms in adulthood preceded dementia in 48% of DLB patients, compared with 15% of Alzheimer’s disease patients and 15% of healthy controls.
Data Source: A case-control study of 509 patients.
Disclosures: The authors reported having no relevant financial conflicts to disclose.
Racial Disparities in HIV Diagnoses Persist
Blacks/African Americans continue to bear a disproportionate burden of HIV diagnoses, compared with any other racial or ethnic groups, according to data published Feb. 3 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Between 2005 and 2008, blacks/African Americans accounted for 50.3% of all HIV diagnoses in 37 states reporting to the CDC through HIV surveillance systems, despite representing just 13.6% of the population in those states, the authors wrote. Additionally, in 2008 alone, the rates of HIV diagnosis among African American males and females, respectively, were 8 and 19 times the rates reported for white males and females and 2 and 4 times the rates reported for Hispanic males and females, they stated.
"In nearly every demographic and transmission category, the largest percentages of HIV diagnoses were among blacks/African Americans," the authors wrote.
For example, during the 4-year reporting period, 56.1% of HIV diagnoses were made in individuals aged 25-44 years, and of this age group, blacks/African Americans accounted for 46.4% of them. Similarly, among adolescent and adult males, blacks/African Americans accounted for the largest percentage of HIV diagnoses overall, at 44.8%, compared with 19% and 33.6% among Hispanic/Latino and white males, respectively. They also accounted for the largest percentage of HIV diagnoses in the South, at 50.1% compared, with 16.5% and 31.7% among Hispanic/Latino and white males, and in the Northeast, at 42.1%, compared with 28.3% and 25.5% among Hispanic/Latino and white males, the report stated.
Among females over the 4-year period, blacks/African Americans accounted for 50.3% of the HIV diagnoses overall, compared with 17.8% and 29.4% for Hispanic/Latino and white females, respectively, and they also accounted for the majority of HIV diagnoses in the South, Midwest, and Northeast, according to the report (MMWR Morb. Mortal. Wkly. Rep. 2011;60:93-8).
When assessed by transmission category, the racial disparities were most pronounced in the rates of HIV diagnoses attributed to heterosexual contact. Nearly 71% of the males in this transmission category were black/African American, while 16.3% were Hispanic/Latino, and 11% were white. Among the females, 68% of those in the heterosexual transmission category were black/African American, compared with 14.3% who were Hispanic/Latino and 15.2% who were white.
Among black/African American males, HIV transmissions were classified as male-to-male sexual contact in 61.1% of the diagnoses, heterosexual contact in 23.1%, injection drug use in 11.9%, and both male-to-male sexual contact and infection drug use in 3.6%, the analysis showed. In black/African American females, 85.2% of HIV transmissions were through heterosexual contact and 14% were through infection drug use, according to the report.
In a trend analysis for the 4 years covered by the report, rates of HIV diagnoses increased among black/African American males while trends in other race/ethnic groups and gender groups remained stable.
"Lack of knowledge of HIV status and missed opportunities to diagnose HIV in routine clinical settings are contributing factors to the HIV epidemic among blacks/African Americans," the authors wrote in their editorial comment. "Ongoing and increased HIV testing and efforts to ensure referral and access to HIV-related primary medical care are warranted," they stated, as are comprehensive approaches "that take into account patient-specific behavioral risk factors, such as having multiple sex partners and unprotected sex, in addition to underlying factors such as poverty, unequal access to health care, incarceration, lack of education, stigma, homophobia, sexism, and racism."
No conflicts of interest were reported.
Blacks/African Americans continue to bear a disproportionate burden of HIV diagnoses, compared with any other racial or ethnic groups, according to data published Feb. 3 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Between 2005 and 2008, blacks/African Americans accounted for 50.3% of all HIV diagnoses in 37 states reporting to the CDC through HIV surveillance systems, despite representing just 13.6% of the population in those states, the authors wrote. Additionally, in 2008 alone, the rates of HIV diagnosis among African American males and females, respectively, were 8 and 19 times the rates reported for white males and females and 2 and 4 times the rates reported for Hispanic males and females, they stated.
"In nearly every demographic and transmission category, the largest percentages of HIV diagnoses were among blacks/African Americans," the authors wrote.
For example, during the 4-year reporting period, 56.1% of HIV diagnoses were made in individuals aged 25-44 years, and of this age group, blacks/African Americans accounted for 46.4% of them. Similarly, among adolescent and adult males, blacks/African Americans accounted for the largest percentage of HIV diagnoses overall, at 44.8%, compared with 19% and 33.6% among Hispanic/Latino and white males, respectively. They also accounted for the largest percentage of HIV diagnoses in the South, at 50.1% compared, with 16.5% and 31.7% among Hispanic/Latino and white males, and in the Northeast, at 42.1%, compared with 28.3% and 25.5% among Hispanic/Latino and white males, the report stated.
Among females over the 4-year period, blacks/African Americans accounted for 50.3% of the HIV diagnoses overall, compared with 17.8% and 29.4% for Hispanic/Latino and white females, respectively, and they also accounted for the majority of HIV diagnoses in the South, Midwest, and Northeast, according to the report (MMWR Morb. Mortal. Wkly. Rep. 2011;60:93-8).
When assessed by transmission category, the racial disparities were most pronounced in the rates of HIV diagnoses attributed to heterosexual contact. Nearly 71% of the males in this transmission category were black/African American, while 16.3% were Hispanic/Latino, and 11% were white. Among the females, 68% of those in the heterosexual transmission category were black/African American, compared with 14.3% who were Hispanic/Latino and 15.2% who were white.
Among black/African American males, HIV transmissions were classified as male-to-male sexual contact in 61.1% of the diagnoses, heterosexual contact in 23.1%, injection drug use in 11.9%, and both male-to-male sexual contact and infection drug use in 3.6%, the analysis showed. In black/African American females, 85.2% of HIV transmissions were through heterosexual contact and 14% were through infection drug use, according to the report.
In a trend analysis for the 4 years covered by the report, rates of HIV diagnoses increased among black/African American males while trends in other race/ethnic groups and gender groups remained stable.
"Lack of knowledge of HIV status and missed opportunities to diagnose HIV in routine clinical settings are contributing factors to the HIV epidemic among blacks/African Americans," the authors wrote in their editorial comment. "Ongoing and increased HIV testing and efforts to ensure referral and access to HIV-related primary medical care are warranted," they stated, as are comprehensive approaches "that take into account patient-specific behavioral risk factors, such as having multiple sex partners and unprotected sex, in addition to underlying factors such as poverty, unequal access to health care, incarceration, lack of education, stigma, homophobia, sexism, and racism."
No conflicts of interest were reported.
Blacks/African Americans continue to bear a disproportionate burden of HIV diagnoses, compared with any other racial or ethnic groups, according to data published Feb. 3 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.
Between 2005 and 2008, blacks/African Americans accounted for 50.3% of all HIV diagnoses in 37 states reporting to the CDC through HIV surveillance systems, despite representing just 13.6% of the population in those states, the authors wrote. Additionally, in 2008 alone, the rates of HIV diagnosis among African American males and females, respectively, were 8 and 19 times the rates reported for white males and females and 2 and 4 times the rates reported for Hispanic males and females, they stated.
"In nearly every demographic and transmission category, the largest percentages of HIV diagnoses were among blacks/African Americans," the authors wrote.
For example, during the 4-year reporting period, 56.1% of HIV diagnoses were made in individuals aged 25-44 years, and of this age group, blacks/African Americans accounted for 46.4% of them. Similarly, among adolescent and adult males, blacks/African Americans accounted for the largest percentage of HIV diagnoses overall, at 44.8%, compared with 19% and 33.6% among Hispanic/Latino and white males, respectively. They also accounted for the largest percentage of HIV diagnoses in the South, at 50.1% compared, with 16.5% and 31.7% among Hispanic/Latino and white males, and in the Northeast, at 42.1%, compared with 28.3% and 25.5% among Hispanic/Latino and white males, the report stated.
Among females over the 4-year period, blacks/African Americans accounted for 50.3% of the HIV diagnoses overall, compared with 17.8% and 29.4% for Hispanic/Latino and white females, respectively, and they also accounted for the majority of HIV diagnoses in the South, Midwest, and Northeast, according to the report (MMWR Morb. Mortal. Wkly. Rep. 2011;60:93-8).
When assessed by transmission category, the racial disparities were most pronounced in the rates of HIV diagnoses attributed to heterosexual contact. Nearly 71% of the males in this transmission category were black/African American, while 16.3% were Hispanic/Latino, and 11% were white. Among the females, 68% of those in the heterosexual transmission category were black/African American, compared with 14.3% who were Hispanic/Latino and 15.2% who were white.
Among black/African American males, HIV transmissions were classified as male-to-male sexual contact in 61.1% of the diagnoses, heterosexual contact in 23.1%, injection drug use in 11.9%, and both male-to-male sexual contact and infection drug use in 3.6%, the analysis showed. In black/African American females, 85.2% of HIV transmissions were through heterosexual contact and 14% were through infection drug use, according to the report.
In a trend analysis for the 4 years covered by the report, rates of HIV diagnoses increased among black/African American males while trends in other race/ethnic groups and gender groups remained stable.
"Lack of knowledge of HIV status and missed opportunities to diagnose HIV in routine clinical settings are contributing factors to the HIV epidemic among blacks/African Americans," the authors wrote in their editorial comment. "Ongoing and increased HIV testing and efforts to ensure referral and access to HIV-related primary medical care are warranted," they stated, as are comprehensive approaches "that take into account patient-specific behavioral risk factors, such as having multiple sex partners and unprotected sex, in addition to underlying factors such as poverty, unequal access to health care, incarceration, lack of education, stigma, homophobia, sexism, and racism."
No conflicts of interest were reported.
FROM MORBIDITY AND MORTALITY WEEKLY REPORT
Major Finding: HIV diagnoses in blacks/African Americans continue to be disproportionately high relative to other racial and ethnic groups.
Data Source: Data from the National HIV Surveillance System representing HIV diagnoses rates for 2005-2008 from 37 states with mature surveillance systems.
Disclosures: No conflicts of interest were reported.